Id

Front 1

Eukaryotic

Back 1

Animalia-Helminth
Protista- Protozoa, Fungi
Plantae- Algae

Front 2

Prokaryotic

Back 2

Eubacteria-Bacteria
Archaebacteria- lack true peptidoglycan

Front 3

Noncellular

Back 3

Virus
Prion-non replicon

Front 4

Archaebacteria

Back 4

Lack true peptidoglycan
Insensitive to protein synthesis inhibitor-antibiotics (Streptomycin and Chloramphenicol)
Normal human flora at 3 sites
Associated with a common human disease

Front 5

Nuclear Membrane

Back 5

Procaryote- absent mostly, only in one genus
Eucaryote- present

Front 6

DNA

Back 6

Procaryote- single, circular molecule, ds (usually)
Eucaryote- many linear chromosomes, exception: mDNA has multiple circular chromosomes.

*Mitochondrial genome: circular dsDNA and utilize nuclear encoded genome DNA polymerase gamma to replicate

Front 7

Division

Back 7

Procaryote- Binary fission- not mitosis. Membrane bound, septal ring structure carries out cell division
Eucaryote- mitosis

Front 8

Sexual reproduction

Back 8

Procaryote- NONE, horizontal transfer
Eucaryote- MEOSIS- sex

Front 9

Cell membrane

Back 9

Procaryote- present but lack sterol
Eucaryote- present but contain sterol

Front 10

Ribosomes

*EXAM

Back 10

Procaryote- 30S+50S= 70S
Eucaryote- 40S+ 60S= 80S EXCEPT mitochondria= 70S

Front 11

Respiratory System

Back 11

Procaryote- present in plasma membrane
Eucaryote- present in mitochondria

Front 12

Cytoskeleton (tubulin, actin, myosin, intermediate filament proteins)

Back 12

Procaryote- present (homologs of actin, tubulin, intermediate filament proteins exist). Need tubulin like protein for cell division
Eucaryote- present

Front 13

Endomembrane/subcellular organelles

Back 13

Procaryote- Absent
Eucaryote- Present (Mito, golgi, vacuoles)

Front 14

Endospores

Back 14

Procaryote- Very heat, chemical, desiccation resistant
Eucaryote- Absent

Front 15

Cell Wall

Back 15

Procaryote- present, peptidoglycan
Eucaryote- ONLY plant, fungi posses polysaccharide cell wall

Front 16

Flagella

Back 16

Procaryote- Present: submicroscopic single repeating peptide
Eucaryote- Present: microscopic (9+2 microtubule arrangement)

Front 17

Surface Translocation

Back 17

Procaryote- Present
Eucaryote- Present amoeboid, pseudopodia

Front 18

Size

Back 18

Virus 0.03- 0.3 um
Bacteria 0.1- 10 um
Microscopic protozoa and fungi 4-40 um

Front 19

Visible light/bright field microscopy

Back 19

Visible light to see bacteria due to contrast diff in bacteria and medium

Front 20

Darkfield Microscopy

Back 20

Reflected light to visualize bacteria too thin to be seen by bright field (e.g. T. Pallidium- syphilis)

Front 21

Simple Positive Stain

Back 21

Stain cell, not extracellular medium

Front 22

Simple Negative Stain

Back 22

Stain extracellular medium, not cell (e.g. india ink stain for visualizing capsules)

Front 23

Differential staining

Back 23

Gram + cell wall's thick peptidoglycan layer retain crystal violet-iodine complex after exposure to ethanol

Gram - thin peptidoglycan layer doesn't retain crystal violet-iodine complex after exposure to ethanol

Front 24

Procedure of differential, positive staining

Back 24

Crystal violet- primary stain; a positive stain
Iodine- mordant/fixative, forms complex w/ crystal violet
Alcohol- decolorizer/destain- differentiate between + and - bacteria
Safranin- counter stain; a positive stain

*Blue/purple +
*Pink/Red -

Front 25

Consistency of gram stain reaction

Back 25

Any genera of bacteria stained by gram stain, all species of GENERA have same cell wall so same grain stain!

Any species of bacteria stained by gram stain, all strains of SPECIES have same cell wall so same gram stain!

*Steptococcus& Salmonella: gram -

Front 26

Variable of staining of gram + bacteria from:

Back 26

1. Variability in staining (purple and red both seen)
2. Peptidoglycan layer structural damage to specific cells
3. Very thin peptidoglycan layers

Front 27

Bacteria too morphologically simple

Back 27

Cannot be identified only by size, shape, cell arrangment, gram stain only, but gram stain help with:
1. DIRECTED/ INITIAL ANTIMICROBIAL THERAPY
2. AID IN IDENTIFICATION OF BACTERIA

Front 28

Acid- Fast Staining Procedure

Back 28

1. Detect cells to Mycobacterium or Nocardia
2. Used to identify clinical isolates to these genera
3. Do not stain by gram staining: not - or +
4. Wall structure more complex than - or +

*stained cell are acid-fast bacilli

Front 29

Genera of Gram + Bacteria

Back 29

1. Actinomyces
2. Bacillus
3. Bifidobacterium
4. Clostridium
5. Corynebacterium and other diptheroids
6. Enterococcus
7. Gardnerella (stain - due to thin cell wall)
8. Lactobacillus
9. Listeria
10. Mobiluncus (stain - due to thin cell wall)
11. Peptostreptoccocus- unclear if genus name survives
12. Propionibacterium
13. Staphylococcus
14. Streptococcus

Front 30

Medically important gram + cocci

Back 30

1. Streptococcus
2. Staphylococcus
3. Enterococcus

Front 31

Cocci

Back 31

Clusters- staphyloccocus
Chains- streptoccocus
Pairs- Streptoccous pneumoniae
Kidney bean pairs- Neisseria

Front 32

Spirochetes

Back 32

Relaxed Coil- Borrelia
Tightly coiled- treponemia

Front 33

Rods

Back 33

Square ends- bacillus
Rounded ends- Salmonella
Club Shaped- cornebacterium
Fusiform- Fusobacterium
Comma Shaped- vibrio

Front 34

Cell shaped determined by:

Back 34

Murein Sacculus (peptidoglycan chain or cluster) and Cytoskeleton

Front 35

Cocci

Back 35

Round, - or +
Diploccocus (pairs): Gram - kidney beans; Gram + lancet shaped
Chains
Clusters

Front 36

Bacillus

Back 36

Rod
Short thin
Long thick
Clubbed Shaped

Random, single cells, pairs (doublet) or chains

Front 37

Helicoidal

Back 37

Curved/comma shaped
Spirochetes

Single cells, pairs, chains

Front 38

Pleomorphic Bacillus

Back 38

Varies in shape and size

Front 39

Gram stain morphology

Back 39

Clinical term used to describe lab results
Include:
1. Gram stain reaction
2. Cell morphology

*Case: Emperic therapy initiated administer Bacterium (common therapy) switched to ampicillin b/c gram + cocci (directed therapy)

Front 40

Bacterial Structure

Back 40

Cell membrane
Genome
Ribosomes
Intracellular macromolecules
Cell wall

Varies: Plasmids, pili, capsules, flagella

Front 41

Bacterial chromosome (nucleoid)

Back 41

Single circular chromosome of dsDNA
Plasmids or prophages may be present
30S + 50S = 70S: required for translation/protein synthesis, site of action of antibiotics

Front 42

Cell surface structures

Back 42

1. Lie on top of/on SURFACE of cell wall and extend from surface into environment
2. Present in both gram + and - bacteria
3. Can lack/ have flagella, pili, capsules but often present
4. Monomeric units, repeated N number of times. Type 2-T independent antigens (capping of naive B cell, not immunogenic, no class switch). Highly variable antigenic epitopes- little cross reactivity between serotypes, not useful for immunity and poor antibiotic range

Flagella
Pili-Fembriae
Capsules- exopolysaccharide
S-layer

Front 43

Flagella

Back 43

H antigen protein- aid in identification of bacteria
Repeating polypeptide units
Not capsules, pili, LPS, or S layer
Virulence factor- chemotaxis- motility to sense enviro

Front 44

Pili (Fimbriae)

Back 44

Protein at end
Repeating polypeptide units (diff than flagella)
Allow bacteria to attach to replicate faster
Virulence factors: adherence to host cells, antiphagocytic, motility (Type IV pili- surface translocation)

*Sex pili in conjugation- transmission of genetic material, spread of antibiotic resistance in bacteria

Front 45

Capsules/ slime layers/ Glycocalyx/ Exopolysaccharide (EPS)

Back 45

Mucoid-like mucous coat around cell which are:
1. Cell surface associated
2. Slime layer (Cell-free/soluble in water)
3. Both cell surface associated and a slime layer

*Vary in same genus and species and can be any composition

*After infection with 1 strain, protective immunity to that strain may not provide protection against infection from another strain with different caps

Usually polysaccharide polymers of repeating units of:
1. Single sugar molecule (e.g. dextran or levan)
2. Complex polysaccharides of sugar, sugar alcohol, aminosugar, sugaracids
3. D-glutamic acid (form a polypeptide: Bacillus anthracis)
4. O-antigen of LPS

Front 46

Biofilms

Back 46

Protected, complex 3 dimensional structure
Community of individual bacterial or yeast cells and microcolonies in mucoid (hydrated) EPS film/flim adhering to wet surface (inert or living)
1/2 of human bacterial esp chronic infections involve biofilm (CDC)
Undergo PHENOTYPIC changes:
1.Motile bacteria sessile (non-motile) when in biofilm
2. Bacteria PERSIST even with antimicrobial agents to which they are susceptible in planktonic (normal) state. Multidrug resistant (MDR) in high conc of antibiotics
3. Cells revert to planktonic form and released back into enviro so thats why some therapies fail. After antimicrobial therapy cleared, nonbiofilm bacteria from body, newly released revertants re-seed human body (RECURRENT INFECTION)
4. Minute releases of compounds produced by bacteria in biofilm can disrupt biofilm and release bacteria in biofilm

Front 47

Medical significance of capsule/biofilms

Back 47

1. Adherence (virulence) to host tissues and surfaces (AKA surface colonization e.g. catheters.
*Biofilm enable bacteria (- & +) & yeast to grow in moving solution
2. Protection against phagocytosis, serum factors, antibodies
3. Protection against antibiotics (absorbed by EPS so cant interact with cells)
4. Protection against desiccation
5. Antigen used to ID agent. Capsule is K antigen- aids in identification of bacteria

Front 48

Cell membrane (plasma membrane)

Back 48

Fluid Mosaic model
Phopholipid bilayer with hydrophilic groups at top/ bottom and hydrophobic in middle
Embedded polypeptides in membrane by divalent cations (Ca2+ and Mg2+). Hydrophobic interaction with FA moiety of phospholipids
NO STEROLS except:
1. Mycoplasma
2. Helicobacter spp
3. Erhlichia
4. Anaplasma spp

Front 49

Cell membrane permeability and transport

Back 49

Differentially permeable
Some nutrients are permeable through membrane
Membrane transport for non-permeable nutrients
Hydrophobic: permeable through CM
Hydrophilic: non-permeable so need transport system

Front 50

Cell membrane contain specific, transport mechanisms to secrete proteins from cell

Back 50

Belong to 1 of 5 transport systems
Type 3 secretion systems [only in bacteria, not humans] (injectosomes) employ conserved multiprotein mechanism by which gram - bacteria inject/insert protein toxins into human cells so bacteria can control human cell functions

Front 51

Cell membrane contain respiration

Back 51

Made of: Electron Transport Chain (ETS), ATP synthase (ATPase)
Produce: ATP, Proton Motive Force (PMF aka ion current)

*Bacteria have no mito

Front 52

Cell membrane contain parts of biosynthetic pathways for cell wall components and for cellular replication

Back 52

SITE OF SEPTUM FORMATION- septal ring

Front 53

Cell membrane contain osmoregulatory and sensory (chemotaxis) mechanisms

Back 53

Bacteria regulate their internal osmotic pressure so bacterial cells are hypertonic to external environment
Chemotaxis: bacteria/cells move toward or away from substance

*Need higher internal than external. Water flow in- burst/swell

Front 54

Gram + cell wall

Back 54

1. Peptidoglycan layer thick
2. Polysaccharide covalently linked to peptidoglycan
3. Lipoteichoic acid polymers anchored in cell membrane through peptidoglycan layer

Front 55

Gram - cell wall

Back 55

1. Outer membrane with LPS
2. Peptidoglycan in periplasm

Acid-fast cell wall?

Front 56

Porin

Back 56

Outer membrane for vaccine

Front 57

Function of cell wall

Back 57

1. Interface between bacteria and its environment
2. Differential staining occurs during gram staining
3. Shield against environmental changes: molecular sieve (screen large macromolecules), prevent cell burst due to increased osmotic pressure
4. Maintain cell shape due to peptidoglycan

Front 58

Peptidoglycan layer

Back 58

Rigid backbone
1. Fabric of woven threads (polymers) that encase cell
2. Polymer (thread)- repeating/alternating subunits of:
*N-acetylmuramic acid (NAM)
*N-acetylglucosamine (NAG)
3. Human lysozyme in saliva and tears cleave aminosugar threads/backbone to lyse bacteria
4. NAM on different polymer/threads cross-linked (covalently bonded) via their peptide stems (aka amino acid side chains). Cross linkage creates fabric.
*all peptide stems have D-amino acids such D-alanine to make peptidoglycan
Structure based on peptide side chain composition, bridge composition, and chemical modification

Front 59

Function of peptidoglycan shell

Back 59

1. Prevent cell bursting from osmotic forces
2. Determine/maintain cell shape

*Rigid peptidoglycan layer limit volume of water that can move into cytoplasm, preventing cell swelling and bursting. Maintain hyperosmotic pressure!

Cell wall turnover during exponential phase growth occurs due to cell wall enzymes like lytic transglycosylases. If product of enzyme released from cell its recognized by TLRs to SIRS

Front 60

Bacteria lack peptidoglycan *EXAM

Back 60

1. Mycoplasma
2. Rickettsia
3. Ehrlichia
4. Anaplasma
5. Chlamdyia

Front 61

Gram - bacterial cell wall

Back 61

*Double track membrane
1. Periplasm- contain thin peptidoglycan layer
2. Outer membrane- lipid bilayer with phospholipid as INNER leaflet and LPS as OUTER leaflet. Resistance to dyes, hydrolytic enzymes and detergents that gram positive bacteria are sensitive to

Front 62

Periplasm

Back 62

Protein-polysaccharide peptidoglycan gel (not space)
Function:
1. Nutrient uptake from OM to CM
2. Sensory (chemotaxis)
3. Degradative enzymes
4. Osmoregulation
5. Osmotic protection but only 1 layer thick (why gram - bacteria are less susceptible to cell wall active agents)

Front 63

Outer Membrane

Back 63

Shield against environmental insults b/c it is differentially permeable to hydrophobic so excludes dyes, detergents, hydrolytic enzymes (lysozyme).
THUS, gram + lack OM so susceptible to dye, detergents, hydrolytic enzymes

Lipid bilayer (not phospholipid bilayer)- differentially permeable

Composition:
1. Lipopolysaccharide
2. Phospholipid
3. Proteins aka outer membrane proteins

Front 64

Lipopolysaccharide (LPS aka endotoxin, exogenous pyrogen)

Back 64

Lipid A + core polysaccharide+ O-antigenic chain

Front 65

Lipid A

Back 65

*Endotoxin
1. Disaccharide
2. Phosphate groups and FA covalently bonded
3. Toxicity of LPS associated with lipid A *

Front 66

Core Polysaccharide

Back 66

Contain sugars, aminosugars, sugar acids, sugar alcohols

Front 67

O-Antigenic Side Chain

Back 67

Terminal polysaccharide of repeated N number of times
Contain sugars, aminosugars, sugar acids, sugar alcohols
O- antigens of enterics
Highly specific: Salmonella vs E. Coli
Highly variable: Salmonella have distinct O antigens, diff LPS, Type 2 antigen

Front 68

LPS

Back 68

1. Structural component of OM
2. Chromosomally encoded
3. Broad specificity
4. Heat stable
5. Does not form toxoids

Front 69

Broad specificity of LPS

Back 69

Effect many organ systems in susceptible host
1. Pyrogencity/fever producing by:
a. IL-1 (endogenous pyrogen: increase body temp)
b. Act directly on hypothalamus (exogenous pyrogen)- disrupts endothelial function -> CNS
2. Activate alternative and classical complement pathway
3. Activate Hageman Factor XIII
4. Induce and release endogenous mediators: TNF alpha, IL-1, IL-6 (primary endogenous mediator), arachidonic acid metabolites, histamines, NO, free radicals esp superoxide anions, bradykinins

Front 70

Heat Stable of LPS

Back 70

Not destructed by boil or autoclaving at 121C
Strong oxidizing agent (sulfuric acid, potassium dichromate) or burning/incineration will destroy LPS

Front 71

No toxoid formation of LPS

Back 71

Primary structure of Lipid A (endotoxin) that is toxic
Only BURNING or OXIDATION disrupts primary structure/detoxify endotoxin vs in exotoxin

Front 72

Endotoxin/LPS/Lipid A

Back 72

Potent imumunomodulatory substance-> systemic inflammatory response syndrome (SIRS) -> Distributive shock (DS)

LPS induce SIRS
SIRS similar to acute inflammation (acute phase response) but on systemic scale with macrophages, PMN, endothelial cells as effector cells

SIRS pathway activated by:
1. Infection: 1/2 of clinical cases esp gram - bacteria
2. Non-infectious(trauma/drug rxns): 1/2 of clinical cases of SIRS

Front 73

Pathway for endotoxin initiation/activation SIRS and DS

Back 73

*LPS bind to human Lipid Binding Protein (LBP) in serum
*LPS-LBP complex interacts separately with:
a. membrane bound CD14 receptors on PMNs, macrophages, monocytes
LPS-CD14 complex bind to membrane bound LPS signal transducer receptor protein/TLR
Signal transduction from cell surface to cytoplasm to nucleus which lead to induction and relase of endogenous mediators (cytokines)
*soluble CD14 receptor present in serum bind to endothelial cell cause dysfunction (leakiness) result in hypotension/vascular leak syndrome i.e. Acute Respiratory Distress Syndrome (ARDS)
ARDS common of DS, NOT SIRS

Front 74

SIRS is 2 or more manifestations of

Back 74

1. Temperature > 38C (fever) or < 36C (chills)
2. Tachycardia (>90 bmp) = increase HR
3. Tachypnea (respiration rate of > 20 bpm)= increase rate of breathing
4. Leukocytosis (>12k/mm3) or leukopenia (<4k/mm3)

Front 75

SIRS-> Sepsis->Severe sepsis-> septic shock.

Back 75

Septic shock consists of 1 or more of 3 overarching pathophysiological:
1. Systemic inflammation
2. Activation of coagulation
3. Inhibition of fibrinolysis
4. Immunoparalysis

Front 76

Systemic inflammation and activation of coagulation

Back 76

Result from Hageman factor XIII which activates the clotting system (fibrin deposition) and fibrinolysis

Front 77

Inhibition of Fibrinolysis

Back 77

Inhibited by plasminogen-activator inhibitor

Result in accumulation of undissolved thrombin in microcirculation (aka Disseminated Intravascular Coagulation DIC) and hypotension ->Multiorgan failure and/ or skin lesions (aka purpura fulminans)

Front 78

Immunoparalysis

Back 78

Patients survive hyperinflammatory phase and enter a stage of protracted immunosupression by:
a. Loss of delayed type hypersensitivity response to + control antigens
b. Failure to clear primary infection
c. New secondary infections develop
d. dormant viruses; cytomegalovirus (CMV) and herpes simplex virus (HSV) reactivated in ill individuals

*Key aspect of sepsis is immunosupression

Front 79

Sepsis

Back 79

Presence of BOTH
1. Proven infection: pneumonia, UTI, Bacteremia
2. 2 or more manifestations of SIRS

*Bacteremia does not = sepsis

Front 80

Severe Sepsis

Back 80

Both:
1. Sepsis
2. Organ failure (one or more organs) AKA
a. Organ dysfunction (OD)
b. Multiorgan dysfunction (MOD)
c. Multiorgan failure (MOF)

Front 81

Septic Shock

Back 81

Both:
1. Severe sepsis
2. Refractory hypotension (circulatory failure)

Front 82

Shock

Back 82

Inadequate profusion of tissues resulting in cell dysfunction/death caused by either:
1. Cardiogenic
2. Vascular obstructive
3. Hypovolemic

Front 83

Distributive Shock aka Warm Shock

Back 83

1. Endothelial dysfunction/capillary leaky- loss of plasma from vascular system into tissue spaces- hypotension
2. Loss of vascular resistance- hypotension
3. Coagulopathy/ DIC
4. Septic cardiomyopathy: reversible, no structural heart damage, low CO, induced by LPS; C5A; IL-1B; TNFa; IL-6

Front 84

Distributive Shock (Hypovolemic shock)

Back 84

1. Fever or hypothermia
2. Chills
3. Leukopenia or leukocytosis
4. Tachycardia and tachypnea
5. Disseminated intravascular coagulation (DIC)
6. Hypotension and shock, cause MOF or MOD or OD

Front 85

Treatment of Shock

Back 85

1. Effect of LPS/ endotoxin on patient is to activate many physiological pathways. No compound is a cure all
2. Control of SIRS/ DS need many treatment and complex
3. Drotecogin alfa
4. Early goal-directed therapy
a. Sepsis resuscitation bundle
b. sepsis management bundle

Front 86

Dortecogin alfa

Back 86

Activated recombinant protein C
Not FDA approved to treatment severe sepsis/shock
Mechanism: prevent clot formation, break up existing clots, reduce inflammation in blood vessels

Front 87

Sepsis Resuscitation bundle

Back 87

1. Measure serum lactate
2. Blood specimen for culture
3. Broad spectrum antibiotics
4. If hypotensive, give fluids, crystalloid or vasopressin
5. Achieve oxygen saturation

Front 88

Sepsis Management Bundle

Back 88

1. Recombinant human activated protein C
2. Corticosteroids
3. Glycemic Control

Front 89

Implementation of therapy protocol

Back 89

Survival increased 52 to 70%
Hospital length stay reduced by 5 days

Front 90

Detection

Back 90

Limulus Amebocyte lysate test & monoclonal antibodies against LPS. Used in pharmaceutical industry

Presence of nanogram amount of endotoxin can be detected

Front 91

Gram + cell wall

Back 91

Thick peptidoglycan
Teichoic acid (covalently bonded to peptidoglycan)
Lipoteichoic acid (outer leaflet of cell membrane)
Macromolecules (Lipoproteins, polysaccharides, protein)

Front 92

Endotoxin

Back 92

1. Bacterial viability in vitro
2. Only produced by gram - bacteria
3. Only chromosomal encoded
4. Cell associated and released upon cell lysis
5. Not protein
6. Sugar phosphate fatty acid- detected by humans
7. Heat stable
8. Not made by bacteria to cause disease in humans
9. If human cells detect LPS to SIRS to DS
10. Exogenous pyrogen- cause fever by crossing blood brain barrier and act on hypothalamus
11. Induce production/ release of endogenous pyrogen (IL-1, TNFa)
12. In human blood lead to sepsis

Front 93

Exotoxin

Back 93

1. Not required for bacterial viability in vitro
2. Produced by gram + and -
3. Chromosomal or plasmid encoded or on temperate bacteriophage
4. Protein macromolecule
5. A toxic chain, B binds to receptors on cell surface
6. Some pathogen produce single exotoxin other produce many toxins, toxin can be limited to strain of species
7. Heat labile (usually)
8. Made by bacteria for bacteria to grow in human
9. Target to cell receptor (cholera-> GM1 ganglioside)
10. Acts directly on host cells
a. Alternation of cell function (diptheria toxin)
b. Cytolysins (Hemolysins) (streptolysins)
c. Molecular mimcry of host receptor/ligands (bordetella pertussis exotoxin)
11. Not exogenous pyrogen, no direct fever
12. Not endogenous pyrogen (IL-1, TNFa) in human
13. Toxemia- presence in human (blood). Solely cause sign and symptoms of disease

Front 94

Gram + Peptidoglycan (50%) of cell wall

Back 94

Present in larger amount
Extensive cross link (muramic acid peptide side chain)
* Both reason for differential gram staining

Medical importance:
Induce production of endogenous mediators (TNFa, IL-6)
Lead to SIRS/ hypotensive shock/ DS

Front 95

DIC and DS

Back 95

Occur in infection caused by etiologic agents lacking endotoxin (LPS):
1. Gram + bacterial infections
2. Fungal infections
3. Viral infections

DIC and DS occur with these agents b/c we have PARS that recognize conserved parts of PAMPS. Also, initiate release of endogenous mediators that cause SIRS.

Front 96

Pathogen Associated Receptors (PARS)

Back 96

Human body can detect infection by diff infectious agents via PARS which bind to PAMP. PARS are:
1. NOD1 and NOD2 (deficiency related to Crohns- irritable bowel syndrome)
2. TLR receptor (11 total, extracell PARS) bind to PAMPS such as: peptidoglycan and teichoic acid polymers from bacteria, N formyl methoinine leucine phenylalaine (1st three N-terminal amino acids of bacterial proteins), CpG nucleotides (unmethylated, normal part of flora), LPS

PARS(part of innate immune system) (human encoded) determine what is and what is not a PAMP (do something that agent needs and detection for infection)

Front 97

Bacterial spores (endospores)

Back 97

Most bacteria do not form spores
Bacterial species can survive adverse conditions
Forms inside mother cell, which dies
Complete but inactive cell in a protective shell
When environmental favorable, spore germinates

Front 98

Bacterial spore Formation

Back 98

Vegetative growth
Forespore
Formation of cortex
Formation of coat
Endospore
Free spore

Front 99

Bacterial spore properties

Back 99

Compared to vegetative cells, increased:
1. Longevity
2. Resistant to heat/temp
3. Resistant to desiccation
4. Resistant to chemical agent

*But burns

Front 100

Spore-forming bacteria

Back 100

Gram +
1. Bacillus
2. Clostridium (Clostridium dificil= bleed from colon)

Medical equipment or surfaces contaminated by spores require special disinfectants or severe sterilization (inhalation equipment)

Front 101

Small Colony Variants (SCV)

Back 101

*NOT BIOFILM
1. Growth deficient variants that form colonies 1/10 of normal size. Deficiencies in energy metabolism (fermentation &/ or aerobic respiration)
2. Formed by both + and - : Staph aureus, Pseudo aeruginosa, E.Coli and UTI
3. Chronic, recurrent infection of: bone, heart, lung, UTI
4. Can revert to normal size and functioning cell hence SCV phenotypic switching and not permanent genetic deficit. Can revert to wild type cell aka phenotypic conversion

Front 102

Properties of virus

Back 102

Bacteria, Chylamidia, Mycoplasma, Ricksettsiae, Virus all yes EXCEPT:

Bacteria do not require living cells
Mycoplasma do not require living cells
Virus do not divide by binary fission, do not have both DNA or RNA, not susceptible to antibiotics

*Exception is mimivirus (mimicking microbe) and CMV contain both RNA & DNA

Mimivirus- largest genome
Hep D virus- smallest genome

Front 103

Virus

Back 103

1. Submicroscopic (30 to 400 nm)
2. Can only grow in human cell media, not like bacteria
3. *Obligate intracellular parasites, infect living cells and of reproducing in such cells only
3. RNA or DNA and protein, possess lipid envelop
4. Definite structure but vary

*Do not always kill host cell they infect

Front 104

Animal Virus

Back 104

Simple organisms
Take over host cells synthesizing machinery
Utilize host enzymes for own replication
Undergo self assembly

Front 105

Virus properties

Back 105

15 to 300nm
Observed by electron microscopy
Package and compress genome, as does cellular life

Front 106

Virus Structure

Back 106

1. Virion
2. Nucleic Acid
3. Protomer
4. Capsomer
5. Capsid
6. Nucleocapsid
7. Envelope

Front 107

Virion

Back 107

Aka infectious virion
Complete viral particle
Infect another host cell and repeat repetitive cycle

Front 108

Viral genome is Nucleic Acid

Back 108

*For any one virus(polio virus, Hep B virus), each infectious virion possess same NA

NA is either:
1. dsDNA
2. ssDNA
3. +ssRNA (AKA positive sense polarity)
4. -ssRNA (AKA negative sense polarity)
5. dsRNA with 2 identical or complimentary strands

Genome is either:
1. Linear or circular structure
2. Condensed by histones or histone like proteins

Front 109

Protomer

Back 109

Protein subunit of capsid
Repetitive polypeptide subunits arranged in symmetric patterns either a or b
a. Protomer -> capsomer-> capsid e.g. icosahedral capsids
b. protomer -> capsid e.g. helical capsids

Front 110

Capsomer

Back 110

In most animal viruses with icosahedral symmetry, protomers are arranged in oligomeric clusters in repetitive symmetrical pattern

Result in cubic or icosahedral symmetry capsids

Front 111

Capsid

Back 111

Protein shell or coat that enclose core of the NA genome and any associated proteins

Front 112

3 forms of symmetry

Back 112

1. Complex
2. Cubical or icosahedral
3. Helical

Core= NA genome + any associated proteins

Front 113

Complex Symmetry

Back 113

Viruses with structures that have not been resolved because the structure are too complex ex: monkeypox

Front 114

Cubic or icosahedral symmetry

Back 114

Icosahedron
Consist of 20 faces
Each face is an equilateral triangle
In most icosahedral viruses- protomers arranged into capsomers-> capsid

Front 115

Helical Symmetry

Back 115

Capsid is copies of a single species of protomer that bind to each other and the ssRNA genome

Each helical virus has specific diameter & length

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Helical structure of a non-eveloped virus

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1. Small segment of full virus particle
2. Protomers assemble in helical structure around NA genome of virus and form nucleocapsid
3. RNA genome extend entire length of virus particle
4. Core of virus particle is hollow

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Nucleocapsid

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Protein associated with NA genome
Capsid together with NA genome plus associated proteins
a. Most virons consist of solely of a nucelocapsid, others consist of nucelocapsid by envelope
b. Nucelocapsid is stable structure resistant to drying, mild acids, detergents

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Envelope

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Viral membrane, if present, covers/encloses nucelocapsid
Composed of:
Virus encoded proteins, 2 important:
1. Peplomer- glycoproteins that form SPIKES on surface of envelope and attach infectious viron to cell receptor
2. Layer between envelope and nucleocapsid that mediates interaction between capsid and envelope:
a. Tegument: Amorphous layer complex functions b/w envelope and nucleocapsid
b. Matrix protein: lattice provide structure of envelope
Host derived lipids and carbohydrates
Membrane derived from:
a. nuclear membrane
b. subcellular organelle (ER, golgi) membrane
c. cytoplasmic membrane
Membrane obtained from host during budding of some viruses

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Enveloped Virus

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Fragile, easily disrupted/denatured e.g. envelope sensitive/inactivated by drying-dessication and detergents

*Environmental wimps but capable of harming human host with infections

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Disruption of envelope of enveloped virus

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Virus inactivation i.e. virus particle no longer infectious (it cant bind to host cell ligands)

Front 121

Transmission of enveloped virus

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Nearly all enveloped virus transmitted:
1. via anthropods (insect vectors)
2. in respiratory droplets
3. In bodily fluids, semen, saliva or secretions
Non enveloped viruses may also be transmitted as above

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Classification of animal virus

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Type of NA acid used for genome
1. DNA (ds or ss) if ss, either + or - polarity
2. RNA (ds or ss) if ss, either + or - polarity

Icosahedral: capsomers arranged in triangles that form a symmetric figure
Helical protomers are arranged in a hollow core that appears helix shaped
Complex undefined symmetry

Presence or absence of envelope: peplomers present?

For viruses with icosahedral symmetry, the number of capsomers is quantitated
For viruses with helical symmetry the diameter of helix and # of turns is measured

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Viral Clades

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Group with descendants from common ancestor
Viral clades (sequence-based subtypes, AKA genotypes) grouped on sequence similarity and diversity among clade members within total viral population
Clades not same as virus serotypes which are based on antigenic diversity
Example:
1. Hepatitis C classified into 6 genotypes (clades) based on phylogenetic analyses of virus. Genotypes differ by 30-50% in their nucleotide sequence
Person with chronic viral infection make population with diverse genomic sequences: quasipsecies. Occur when person infected with virion belonging to 1 clade e.g. HCV
Clinical implication is immune evasion

Clade result from poor proof reading by viral polymerase which lead to multiple changes in sequence of viral genome followed by interaction w/ natural selection/ environmental host factors

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Virus Replication Cycle

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1. Attachment
2. Penetration
3. Uncoat
4. Macromolecule
5. Assembly
6. Release
7. Spread

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Attachment

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Virus ligand binds to specific host cell receptor
Virus-receptor interactions are major determinant of infectivity
Specificity of attachment determines both:
1. Host range of virus (humans or humans AND animals) via LOW affinity receptors
2. Tissue tropoism (where in body virus replicates) via HIGH affinity receptors

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Penetration

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Virion can enter cell by:
1. Direct penetration
2. Surface eclipse- pH independent cell entry
3. Receptor- mediated endocytosis- viropexis- pH dependent cell entry

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Uncoating

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Removal of protective coats with release of viral NA
1. Infectivity is lost AT THIS POINT
2. Target of antiviral therapy for at least one virus

*Infectivity of wall
Blocked by antiviral therapy- amantidine & rimantidine inhibit flu virus uncoating

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Macromolecular synthesis aka eclipse phase

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Synthesis of viral-encoded proteins and viral genome
Virus need to make more virus by making more genome and proteins
1. DNA virus replicate in nucleus (exception: poxivirus)
& RNA virus replicate in cytoplasm (exception: influenza)
2. + sense ssRNA, - sense ssRNA and dsRNA virions ALL must encode for RNA - dependent RNA polymerase enzyme (RNA POL) to make antisense RNA to produce viral genome (+ sense ssRNA)
a. Exception: Retroviruses (HIV) have reverse transcriptase (RNA dependent- DNA polymerase) which transcribe the +ssRNA to DNA then mRNA is transcribed from viral specific DNA. This is target for many anti-HIV drugs (AZT)
3. - sense ssRNA and ds RNA infectious virions MUST contain functional proteins (RNA - dependent RNA polymerase) to make mRNA and process gene that codes for protein

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For virus entering cell to replicate itself, must synthesize:

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NA= its genome
Proteins
Unsurp host cell derived envelope, if appropriate

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RNA virus use one of 4:

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1. +ssRNA
2. -ssRNA
3. dsRNA
4. Retroviruses are the exception: encode and carry in virion (reverse transcriptase, RNA dependent DNA polymerase)

*Retroviruses- transcribe viral RNA genome to DNA

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Assembly

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Viruses auto-assemble (self assemble)
Parts have built in affinity for other parts

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Release aka egress

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Target of antiviral therapy for at least one virus
3 forms of release
1. Lysis of infected cells
2. Slow release without lysis
3. Budding: Viral encoded glycoproteins &/ matrix proteins cluster in membrane and displace host-encoded proteins. Nucelocapsid bind to these proteins and enveloped virions released into extracell enviro

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Spread

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Human virus spread cell-to-cell 4 times faster than expected (HSV-1 and Vaccina Virus)
Early after vaccinia infect cell, it expresses 2 viral proteins on cell surface, which marks cell as infected
When further virus particles reach infected cell, proteins cause host cell to push out actin tails/projections which drive virus particles away toward other cell
Infectious virions bounce from once cell surface to another until they land on uninfected cell

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Viral- Human cell host interaction

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Portal of entry (POE)
How virus gets into body?
Mode to control transmission of infections agents:
Aerosol 1st most difficult
Ingestion 2nd most difficult

Infectious dose required to cause infection= virulence of viral agent

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Primary replication

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Sites in host where 1st replication occurs
Is it near the POE? Relates to incubation period

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Secondary replication

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Sites in host where replication occurs after spread from primary site, not all viruses have secondary replication cycle

*Signs and symptoms may only occur during primary &/ or secondary replication

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Spread within host

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SOME viruses spread from primary site or POE
LOCAL SPREAD ALWAYS OCCURS
Can occur:
Via cell to cell within tissues
via blood stream
via nerves
transplacental

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Tissue Tropoism

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Specificity of virus for particular host and tissue
Major determinant of infectivity

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Types of infections

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1. Productive Infections
2. Persistent infection without cell death

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Types of infections *EXAM

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Virus-host cell interaction = productive & persistent
All human viruses that sucessfully replicate in humans result in productive infections but only SOME human virus produce persistent infections

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Productive Infection *EXAM

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1. Sustained release in absence of lysis (viruses dont always kill the host cell they infect e.g. rhinovirus
2. Lytic infections- viral replication results in host cell death via modifications/damage of host cells
a. Inhibition of host cell macromolecular synthesis
b. Cytopathic Effect (CPE) of viral proteins on host cells (toxic to cells)
c. Inclusion bodies and cell fusion (syncytia formation)
d. Chromosomal alteration can oncogenesis formation
e. Induce apoptosis

*Both result in signs and symptoms but only lytic can cause death

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Persistent infection without cell death *EXAM

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1. Latent-persistent infections: acute episodes of disease between which there is an absence of infectious particles (Herpes simple virus, Varicella- Zoster)
2. Chronic- persist infections: continued presence of virus, disease may be absent (CMV, Human herpes 6 & 7 Hep B) or associated with late immunopathologic disease (HBV-> cirrhosis of liver)
3. Slow- persistent infections (RARE): Following long incubation period, slowly progressive, lethal disease occurs (subacute sclerosing panencephalitis SSPE). No infectious virion may be detected

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Outcomes of Infection *EXAM

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1. Most common outcome: asymptomatic infection with seroconversion (detectable antibodies to microorganisms in blood serum as a result of infection or immunization)
2. Symptomatic infection
3.Virus infect host and may or may not cause disease (signs and symp) but then host mounts an adaptive immune response and infection halted
4. Death of host

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Tumor (Neoplasm)

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Mass of new tissue which persist and grow independently of its surrounding structure

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Transformation

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Conversion of a cell from restricted growth to unrestricted growth
Characteristic of tumors

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Transformed Cell

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1. Loss of contact inhibition i.e. unregulated cell growth, unrestricted growth
2. Appearance of new antigens e.g. tumor specific antigens
3. Metabolic and genetic changes

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RNA tumor virus

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Human T cell leukemia virus (HTLV; lymphotrophic retrovirus) that target the T-helper cell
Adult T cell leukemia caused by HTLV-1

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DNA tumor virus

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Human papilloma virus (HPV)- cervical cancer
Epstein-Barr virus (EBV)- Burkitts lymphoma, nasopharyngeal carcinoma
Hepatitis B Virus (HBV)- primary heptocellular carcinoma

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Viral agents of benign neoplasms

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Different than malignant neoplasms
New growth remains organized and doesnt invade adjacent tissue and undergo metasis)
Human wart viruses- Verruca lesions (skin warts)
Poxvirus- Molluscum contagiosum

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Fungi

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1. Eukaryotic cells (treatment toxic, prokaryote: antibiotic) that reproduce sexually &/ or asexually via spores
2. All are heterotrophs that don't ingest food but absorb nutrients by parasitizing living organisms or degrading dead organic matter as saprobes (saprophytic growth)
3. Most obligate aerobes, but YEAST forms are facultative anaerobes

*Fungi can form SPORES

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Fungi structure

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Cell wall, not peptidogylcan
1. Cell wall complex, contain polysaccharide (glucan, chitin) and glycoproteins
2. Cell membrane contain ergosterol or sterols and is at site of action of anti-fungal agents
3. Some fungi encapsulated- Cryptococcus neoformans

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Fungi distinguished based on:

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Morphology of spores and hyphal elements vs bacteria which use staining reactions, cell & colonial morphology

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Fungi grow in 2 basic forms

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1. Molds
2. Yeasts

*Forms not mutually exclusive- can have one or both

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Molds/ Mycelial (aka saprobic) growth

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1. Spores germinate to produce cell forms- branching filaments: HYPHAE
2. Hyphae divided into cells by SEPTA
3. Growth occur by elongation of hyphae to form mass of hyphae: MYCELIUM

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Yeast

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1. Spore germinate to produce one, round to oval-elongated single cell
2. Reproduce by budding
3. For some yeast (Candida), buds remain attached to mother cells, elongate to cylindrical form: PSEUDOHYPHAE- superfically appears by light microscopy as hyphae

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Thermally dismorphic fungi

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1. Yeast form (parasitic form) in host or in vitro at 37C
2. Mold form (saprobic form) in environment in vitro or at 21-> 24C
Include:
1. Histoplasmosis
2. Blastomycosis
3. Coccidioidmycosis
4. Sporothricosis

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Molds: Conidia

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Naked spores, not enclosed in structure
1. Macroconidia: large spores, too large to reach alveolar spaces. Cant cause RT disease by inhalation. Infectious form of fungi/dermatophytes that infect skin.
2. Microconidia: small spores, small enough to reach alveoli when inhaled and infectious form of systemic fungi in enviro (at 21-> 24C)
a. H. capsulatum
b. B. dermatitidis
c. Aspergillus spp.
d. Murcormycoses

a-d: spread throughout body, treat with toxic drugs
c&d: CMI deficient- catostrophic infection

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Molds: Arthrospores

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Thick- walled spores by hyphal cells
Can cause RT infection
Infectious form for systemic infections (Coccidiodies spa.) in environment

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Molds: Sporangiospores

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Spores within sac-like structures (sporangia/ aka spherule) form that occurs in humans during infection/disease (Coccidioides and Pneumocytis)

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Yeast: Blastospores

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Buds that arise from yeast cells

Front 161

Immunity of fungi

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Cell mediated immunity for control of systemic mycotic infections
PMN needed for other fungi

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Symbiosis

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Close association of 2 different organisms

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Mutualism

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Beneficial association to both

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Commensalism

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Beneficial association for one without effecting the other

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Parasitism

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Beneficial association for one and detrimental for other

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Parasites

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Eukaryotic- Animal Kingdom
Lack cell wall
May have cell wall on cyst forms
Possess flexible cuticles or chitinous exoskeletons

Protozoa: Microscopic. Single cells many protozoa cause human infections are obligate intracellular parasite

Helminths: worms
Anthropods: chitininous exoskeletons (mice, lice, ticks)

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Definitive Host and Intermediate Host *EXAM

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Definitive: Harbors adult or SEXUAL stage of parasite
Intermediate: ASEXUAL stage

*Definitive and intermediate not always human. In some disease humans are intermediate host and for others, humans are definitive host

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Clinical aspects of parasitic infections

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1. Where agent travels in host
2. Organ/tissue infected
3. Host immune response to infection

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Bacteria

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Large metabolic capacity to consume and/or utilize organic compounds for their ability to survive and thrive under difficult conditions

Bacteria can produce fulminant infections (begins sudden, worsen quick)

Microorganism's phenotype determined by genotype, environmental factors (nutrients, gases), physical (pH, temp). Need diff phenotypes b/c more likely to compete, diff replication

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Bacteria's large metabolic capacity to consume enormous due to:

Back 170

-large surface to volume ratio
-close contact with enviro
-accumulate nutrients quickly
-grow rapidly

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Heterotrophic metabolism

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1. Heterotrophs utilize organic molecules as source of building blocks used in synthesis of all cell parts
2. Cellular energy from oxidation of organic compounds
3. All bacteria which cause disease in humans are heterotrophs (KNOW)

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Growth requirements for heterotrophs

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1. Organic molecules are utilized, carbs, protein, lipid
2. Optimum growth temp
3. Inorganic requirements
4. pH optimum is physiological
5. Oxygen

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Temperature requirements

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Optimal growth occurs closer to the max than the minimum temp
Temp minimum determined by reduced enzyme activity and reduced membrane fluidity
Temp max determined by protein denaturation

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Optimum growth temperature

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1. Meosphiles- growth occurs at 20- 55C
*Most pathogens are mesophiles & grow best at 35-36C
2. Thermophiles (obligate or facultative) grow at >55C
KNOW 3. Psychrophiles or cryophiles (obligate or facultative) grow at temps < 20C. Human pathogens are facultative psychrophiles
4. Medical significance is that refrigeration is NOT acceptable method of maintaining sterile conditions

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Inorganic requirements

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Major/ trace inorganic requirements are of cellular life
Trace element requirements are any cellular life would require
Special ionic requirements
Medical significance of inorganic ion requirements: Low or elevated levels of ions serve as trigger/signals for pathogens e.g. low levels of Fe+++ induce Corynebacterium diptheriae to produce diptheria toxin

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pH

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Bacteria grouped by pH, around 7

Front 177

Obligate aerobic organisms

Back 177

Grow in presence of o2

Front 178

Microaerophilic organisms

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Grow when reduced o2

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Facultative anaerobic organisms *EXAM

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-many pathogens are facultative aerobes
-use aerobic respiration for growth when o2 is present bc respiration is more efficient than fermentation
-grow fermentatively when 02 is absent
- Facultative anaerobes responsible for human infections
*early in infection number of bacteria low, o2 plentiful and bacteria respire and replicate
*as number of bacteria increase, they consume o2 so rapidly that o2 levels in infection site drop to zero, bacteria must use fermentation for continued growth

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Aerotolerant anaerobic organisms

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Grow when o2 but grow best in absence of o2 and only use fermentation

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Obligate anaerobic organisms

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Only grow in the absence of o2 and only use fermentation for growth

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Effect of 02 on anaerobes *EXAM

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1. All bacteria generate toxic agents in presence of 02 such as O2- and H2o2 during cellular metabolism but NOT in absence of o2
2. O2- and H202 inhibit cell growth or cause cell death
3. Bacteria are o2 tolerant (aerobes) bc they produce enzymes which detoxify these agents
- superoxide dismutase (SOD) detoxify O2-
-Catalase detoxifies H202

superoxide anion -> SOD-> H202 +o2
hydrogen peroxide -> catalase-> 2H20 + o2

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Oxygen intolerant (obligate anaerobes)

Back 183

Bacteria are o2 intolerant b/c if these bacteria attempt growth in presence of o2, they produce these toxic o2 agents a natural by products of metabolism but lack enzymes to detoxify them
These toxic agents kill bacteria
Obligate anaerobes dont possess catalase & SOD so they can ONLY grow in absence of o2

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Heterotrophic metabolism

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Organic carbon serves as sources of energy and carbon
2 forms:
1. Respiration
2. Fermentation

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Catabolism

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Enzyme mediated-oxidation of complex, reduced carbon molecules (e.g. glucose) to simpler, oxidized forms (small carbon compound or CO2), which may result in energy production

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Respiration

Back 186

UNIQUE enzymatic process b/c process must occur in membrane vesicle or sack (enzyme membrane complex). Wont work unless in sac.

Provide energy in form of ion current or gradient/ PMF so ATP synthesis/production that occur during conversion (recycling) of NADH2 (reduced form) to NAD+ (oxidized form)

*Convert glucose to CO2 by adding H20
*Take in glucose send to mito where resp
* respire bc take o2 and use as terminal electron receptor

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Respiration occur in 2 parts:

Back 187

1. Electron Transport Chain (ETC) transfers electrons & hydrogen ions from NADH2 to terminal electron acceptor (TEA) generating both PMF & reduced TEA
2. ATP synthetase uses PMF to synthesize ATP from ADP & inorganic phosphate

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Aerobic Respiration

Back 188

AKA oxidative phosphorlyation
O2 serve as TEA for ETC, which is reduced to H20 by ETS
Common pathway among pathogenic microorganism/human

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Anaerobic Respiration

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Inorganics (nitrate, sulfate) serve as TEA for ETC
Medical significance:
-Methemoglobinemia (MetHb) occurs when elevated levels of NO3 occur in drinking water
-GI tract normal flora (bacterial) convert NO3 (serves as TEA) -> NO2 if absorbed into blood stream -> MetHb
-MetHb is risk to all humans, esp unborn child

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Fermentation

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-Simpler process than respiration, NOT respiration
-Result in incomplete oxidation of carbon substrate
-Utilize substrate less efficiently than resp, but efficient enough for fermentative bacteria to grow and thrive
-Pathways occur in cytosol, NOT in membrane vesicle
-Doesn't directly produce PMF/ion gradient

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Catabolic pathways

Back 191

Utilized to partially oxidize organic matter
End product of pathways serve as substrate for specific fermentative pathways which generate specific end products via enzymatic steps

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Fermentation pathways

Back 192

Are catabolic pathways
Organic compounds serve as electron donors and electron acceptors
1. Occur in cytosol, NOT in cell membrane (membrane sac not as critical b/c cyotosl)
2. Substrate level phosphorlyation generate ATP
3. Substrates partially oxidized, generating end products
-are 1,2,3,4 carbon compounds and some Co2
-serve as electron acceptor (accept e- & H+ from NADH2) during conversion (recycling) of NADH2 to NAD+
- excreted/released from cell (e.g. pyruvate -> ethanol +CO2)

*Reduced NAD has to be recycled
*Fermentation: kicks end product out of cell
*Throws energy away, reduced NAD out

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Clinical significance of microbial end products via fermentation

Back 193

1. Dental carries by bacteria that produce lactic acid
2. Acidification (acidic pH) of skin and vagina by bacteria which produce propionic acid
3. Abscess are acidic and anaerobic due to fermentative metabolism of bacteria in abscess
-Antibiotics not effective at low pH
-Antibiotics bind to NA and unavailable to harm bacteria
-Low pH kills viable human cells, releasing compounds that bacteria require for growth (e.g. paraaminobenzoic acid- so sulfa drugs dont work)

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Microbial alkaline products that are NOT fermentative end products

Back 194

Proteus spp
-responsible for UTI
-release extracell enzymes (UREASE)

Urease hydrolyze urea in urine, producing NH4+ & CO2
NH4+ raise pH of urine from 6 to above 7
Ca2+ and NH4+ form salt which precipitate, forming calculi (kidney stones)
Salts in urine precipitate at alkaline pH

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Helicobacter pylori

Back 195

cause type b and duodenal ulcers
produce urease which cleave urea to Co2, NH4+, raise microenvironment pH of stomach mucous lining so H. pylori can grow

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Biosynthetic pathway of petidoglycan backbone of cell wall *KNOW

Back 196

Provide basis of selective antibacterial action of chemotherapeutic agents

Front 197

Peptidoglycan is synthesized as:

Back 197

Synthesis of amino sugars/peptidoglycan subunits in cytoplasm, UDP bind to glucose and glucose is converted into NAM and NAG (separately)
1. Uracil diphosphate (UDP) is cytoplasmic tag for directed synthesis of subunits
2. NAG or GlcNAC and NAM or MurNAC synthesis occurs while covalently bonded to UDP
3. Peptide side chain of NAM is synthesized by individual enzymes which add each aa separately

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Peptidoglycan is synthesized as:

Back 198

Assembly and translocation of peptidoglycan subunits through CM
Complete peptidoglycan subunit (MAN-NAG) assembled and bound to bactoprennol then translocated across CM:
1. Petidoglycan subunit is formed by sequential transfer of NAM/ MurNAC then GlcNAC from UDP to bactoprenol (Lipid P, carrier lipid of CM) with UMP release
2. Peptidoglycan subunit shuttled through CM to the growing end of peptidoglycan chain

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Peptidoglycan is synthesized as:

Back 199

Addition of complete peptidoglycan subunit growing end of peptidoglycan chain (aka transglycosylation) occurs via transglycolase (enzyme that make thread) enzyme

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Peptidoglycan is synthesized as:

Back 200

Final cross linking (transpeptidation) of peptide stems is done by *KNOW transpeptidase (aka penicillin binding proteins). 2 amino acids subunits are covalently bonded (an aa from each peptide side chain). This completes synthesis of fabric shell around bacteria providing mechanical strength & rigidity to peptidoglycan

*In cytoplasm, cytoplasm hydrophilic; cell membrane hydrophobic

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Growth

Back 201

Dependent on:
1. Nutrient conditions
2. Cultivation conditions
3. Genotype that encodes for catabolic and anabolic pathways

Front 202

Growth curve

Back 202

Growth of population of pure culture of bacteria in liquid medium (i.e. in vitro) plotted log number of bacteria produced vs time for growth

Front 203

1. Lag Phase

Back 203

Initial phase of growth cycle
When cell volume and mass increase, chromosome replication (DNA synthesis) begin but no cell division takes place
No change in cell numbers

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2. Exponential/ log phase

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When balanced growth occurs
Cell number, mass, volume and amounts of cell components increase by same exponential factor
Expressed as generation (aka doubling/replication) time (GT) i.e. time required for one bacterium to divide into 2 cells = time required for cell to replicate

Front 205

3. Stationary phase

Back 205

No net increase in cell numbers occurs

Front 206

4. Death phase

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Cell death occurs at logarithmic rate
Most bacteria autolyse when they die

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Etiologic agent's replication rate and clinical implications *EXAM

Back 207

1. A rapid growing organism produces acute disease by rapid onset and rapid progression (hrs [fulminant] to days) -> high antigenic dose, strong immune response

2. Slow growing organism produces chronic disease by slow (indolent or insidious) onset and progression) -> [low antigenic dose, weak immune response]

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Short mean generation time (GT)

Back 208

Bacteria produce fulminant (rapidly progressing) infections and high Ag dose (strong immune response may be good or bad for host)

Front 209

Long mean GT

Back 209

Bacteria produce chronic infections and low Ag dose (a weak immune response may be good or bad for host)

Front 210

Effect choice of chemotherapeutic agents

Back 210

1. Inhibitors of protein/petidoglycan synthesis more effective against fast growing than against slow growing organisms
2. Organisms in stationary phase less sensitive to effects of antimicrobial agents

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Note

Back 211

Gram stain reaction or metabolism (aerobic or anaerobic respiration or fermentation) or external cellular structures (flagella) or spore production determine generation time THUS dont effect growth rate

Front 212

Bacterial variation occur by

Back 212

1. Phenotypic variation
2. Genotypic variation

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Genome

Back 213

Physical structure
Consists of chromosome or all chromosomes plus any extrachromosomal elements (plasmid)
Crucial for organism

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Genotype

Back 214

Complete listing of all genes present in an organism

Front 215

Phenotype

Back 215

Complete listing of all physical characteristics that an organism express under defined conditions

Front 216

Replicon

Back 216

DNA or RNA molecule that control its own replication so capable of self duplication

Front 217

Extra Chromosomal Elements (ECE)

Back 217

Replicons that are present in cell, excluding host cell DNA, and include plasmids and bacteriophages

Front 218

Plasmids

Back 218

-Form of ECE present in bacterial cells
-Double stranded covalently closed circular DNA which reside in bacterial cytoplasm
-Replicons, control their own replication
-Control their copy # (# of copies present/cell)
-Replicate in cytoplasm of host bacterial cell utilizing bacterial DNA replication machinery
-Posses a host range (wide vs narrow): some plasmids only replicate in gram + some in gram - & others only in one genus of bacteria
-Not all same, they differ in genes they carry
-Code for ancillary information. Information not required for cell viability in absence of selective pressure (e.g. antibiotics resistance, virulence factors). Housekeeping genes are required for viability!
-Acquired or lost from bacterial cells b/c plasmids encode for ancillary info and metabolic burden on host

*Not all plasmids carry all genes*

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ALL bacterial cells

Back 219

Possess a genome
Single, double stranded
Covalently closed (no free ends) circular chromosome
Encode for all house-keeping genes (those required for normal cellular function)

Front 220

Some bacteria

Back 220

Possess plasmids
Double stranded
Covalently closed (no free ends) circular DNA
Smaller than chromosome
Plasmids encode for ancillary genes

Front 221

Resistance plasmid R1

Back 221

Plasmid encodes resistance to multiple antibiotics (aka resistance determinants)
Antibiotic resistance genes are carried both on IS (insertion) element and transposons within IS

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Bacteriophages

Back 222

Virus replicons (DNA or RNA) which infect bacterial cells
Exist in latent state as a prophage in bacterial cells
Prophage exist as:
plasmid in bacterial cytoplasm (i.e. ECE)
Integrated into bacterial cells chromosome
Bacteriophage designed to recognize receptors on bacteria (No bacterial receptors on human cells)

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Genetic apparatus of bacteria

Back 223

Bacterial chromosome- structure, size, number.
1 covalently closed, circular dsDNA
ECE include:
-Plasmids
-Bacteriophages

Front 224

Phenotypic Variation

Back 224

All cells in a population respond to environmental stimuli in same fashion and produce new/ altered phenotype via expression of genes
No genotypic variation is involved

Front 225

Genotype & phenotype

Back 225

Genotype encode for more traits than that currently expressed at one time
Expressed phenotype less than the full potential encoded by genotype
1. Why do microorganism maintain this potential? B/c they are exposed to radically diff enviros that require diff phenotypes
2. Why does microorganism not express entire phenotype at one time? It could but that requires ALOT expenditure of energy and cell mass. Microorganisms that express only those genes needed for enviro would out-compete those microorganisms that express their entire phenotype at one time

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Genotypic Variation

Back 226

Alteration in cell or cell genome
Event in which genome (genotypes) of one or more cells altered in such a way that the altered cell possesses a new phenotype (i.e. has acquired a unique trait not previously expressed by that population)

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Genotypic variation occurs by 2 different processes:

Back 227

Internally (No foreign/donated DNA is involved) by mutation
Externally by horizontal gene transfer (Don't create new genes) - acquisition of gene from external sources
1. Transformation
2. Conjugation
3. Transduction (generalized/abortive transduction and lysogenic conversion)

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Mutation (internal change)

Back 228

Change in nucleotide sequence of a gene/ genome
Occurrence of mutations is rare but # of bacteria is large
Many mechanisms create mutations
Many types of mutations occur
Bacteria bearing beneficial mutations naturally selected
Clinical mutations (eg. antibiotics resistance) occur and selected for (become dominant/common in population)

* Mutations create new genes but its not a mechanism to transfer new gene
*HGT transfers pre existing genes from one bacterium to but never creates new genes
*Mutations and HGT together are powerful force that allow many unrelated bacteria to gain the info required to survive in hostile enviro

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Horizontal Gene Transfer (external acquired genetic info)

Back 229

Transfer of genetic material from one bacterial cell (donor) to another cell (recipient)
Bacteria exchange transfer of info by 3 mechanisms:
1. Transformation
2. Transduction (generalized or lysogenic conversion)
3. Conjugation

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Transformation

Back 230

DNA fragments released by donor cell autolyze accumulated by recipient cell

Bacterium (donor) become free donor DNA and recipient incorporates free donor DNA into its genome

Front 231

Transduction

Back 231

Abortive phages carrying donor cell chromosomal fragments transfer their DNA to recipient cell

Bacterium (donor) -> viral genome-> viral replication -> progeny virus carrying bacterial DNA -> collaborative phage -> abortive phage

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Conjugation

Back 232

Donor cell plasmid encodes for mechanism to transfer a copy of itself to recipient cell which lacks plasmid

Direct transfer of plasmid ssDNA from donor to recipient-> seperation of mating bacteria

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External genetic info from donor cell is

Back 233

1. Carried on: plasmid, generalized/abortive bacteriophage, lysogenic bacteriophage
2. Naked/free DNA in solution. DNA is either plasmid or fragment of donor cell genome/chromosome

Front 234

External genetic info is exchanged when:

Back 234

1. Homologous genes (chromosomal or plasmid genes of altered function) from donor replace via recombination
2. Plasmid carry new/altered gene reside in recipient cell
3. Latent bacteriophage/prophage (carrying new or altered genes) reside in recipient cell by either:
-integrating into recipient cells chromosome
-function as plasmid in recipients cytoplasm

Front 235

HGT resulted in transfer of antibiotic resistance and virulence factors among bacteria: ACINETOBACTER BAUMANNI

Back 235

1. Major cause of hospital acquired infection
2. Cluster of 45 genes encode for antibacterial drug resistance on resistance island- resistance genes clustered together on chromosome
3. Acquire resistance genes quickly- now resistant to wide range of antibiotics
4. Prone to pick up foreign DNA from other bacteria. Origin of resistance genes traced to other bacteria

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Transformation

Back 236

Uptake of naked/extracell DNA (a DNA fragment) by recipient cell by a mechanism encoded for by the recipient cell

Donor cell lyse, release DNA, free into enviro/solution
Recipient accumulate/take up extracell DNA of any origin

*Not all bacterial genomes encode for transformation machinery, not all DNA can be utilized after transformation

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HGT by transformation

Back 237

Only competent cells are able to be transformed. 2 types of competent cells
1. Naturally competent: chromosome of recipient bacterial cell contain genes that encode for extracell DNA

Front 238

Conjugation

Back 238

HGT of DNA from donor bacterial cell to recipient bacterial cell by mechanism encoded by conjugative (transmissible) plasmid present in donor cell

Donor cell plasmid transfer copy of itself (plasmid) to recipient cell which lack plasmid

Incidental transfer of donor cell chromsomal DNA rare and may not be possible

Donor cell carriers conjugative (transmissible) plasmid which encode for mechanism
1. Cell to cell contact needed (cells mate)
2. DNA copy of plasmid transferred from donor to recpient cell
3. Both single stranded DNA strands (in mother and daughter cell) made ds and process complete

*Conjugative plasmid and transposons have limited host ranges

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Transduction

Back 239

HGT of genetic info (chromsomal or plasmid) from one bacterium to another bacteria by bacteriophage

Front 240

Virus replication

Back 240

Viruses that replicate in bacteria classified based on how they replicate in bacteria

Front 241

Lytic phage

Back 241

Infects bacterial host cell to generate a productive infection (make more phage/produce many new copies of bacteriophage) by:
1. Binding to specific component on cell surface
2. Penetration of phage NA (DNA or RNA) in cytoplasm
3. Replication of phage NA occurs
4. Transcription & translation of phage core & coat genes
5. Phage parts self-asssmble into infectious particles
6. Host cell release new infectious particles- virus into medium

*Productive viral infection always result in infectious virions and in a lytic infection, with lysis of host cell

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Temperate phage

Back 242

1. Bind to specific component on cell surface
2. Penetration of phage NA (DNA or RNA) in cytoplasm
3. After penetration, PHAGE can
a. Undergo normal lytic cycle like 1+2
b. Can become latent

Front 243

Latent phage

Back 243

1. Latency involve repression of phage genes which code for lytic (AKA productive) cycle of phage replication
2. Latent virus (prophage) will do one of 2 things
a. some viral species reside as plasmids
b. other viral species integrate into host cell DNA
3. In either case, prophage DNA replicate in synchrony with host cell DNA and passed on to daughter cells
4. Bacterial strains with prophage DNA as lysogenized
5. Latency ends when depression of phage genes result in phage replication and lysis of host cell

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Temperate bacteriophage replication cycle has 2 options

Back 244

1. Lytic cell will result in productive viral infection with lysis of host cell
2. Viral reproduction occur by replication of lysogenic virus genome and partition to each daughter cell

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2 types of transduction

Back 245

1. Generalized/abortive transduction
2. Lysogenic conversion

Front 246

HGT by transduction/bacteriophage

Back 246

Vector (bacteriophage) determine form of transduction

Limitation of transduction: host range of phages.
Doesnt require RecA

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Generalized (abortive) tranduction

Back 247

Can be lytic or temperate
Occur with defective phage particles of both lytic and temperate phages (note: temperate bacteriophage must be its lytic cycle
During viral replication, donor genome sheared into fragments-> donor cell to lyse
Sheared DNA or intact plasmid randomly packaged into virus particles called PSEUDOVIRIONS/ABORTIVE PHAGES:
-Function as normal infectious virion
-attach to receptor on uninfected recipient cell then packaged DNA introduced into recipient cell cytoplasm
Psedu/abortive phages function a normal infectious virion

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Lysogenic conversion

Back 248

Mediated ONLY by temperate bacteriophage (recipient infected by temperate virus that is in its latent cycle

Bacteria possess new phenotype due acquisition of a prophage (latent bacteriophage) which encode for new phenotype

Prophages carry genes for toxin production: Diphtheria toxin of Cornynebacterium diphtheria

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Genome consist of:

Back 249

Conserved core gene pool
Encode proteins that play roles in cellular functions/house keeping genes (e.g. translation, metabolism, architecture)
Exhibit homogenous G+C contents and codon usage

Front 250

Genome consist of:

Back 250

Flexible gene pools
Vary in size. Depend on bacteria i.e. # of genes within cell in flexible pool from 18% to <1% of total genome
Encode for functions not essential for growth but advantages under conditions (changes in enviro)
Can be transferred laterally by HGT
Gene pool consist of genomic islands (>10kb), genomic islets(<10kb), prophages carrying genes that aid in bacteria adaption, plasmid

Front 251

Genomic Islands

Back 251

Survival of organism under adverse conditions (confer on an organism fitness to occupy ecological niche)
GI with pathogenesis is pathogenecity island and carry type 3 and 4 secretions
GI contain antibiotic resistant genes aka antibiotic restistance island

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Cidal/cide

Back 252

Irreversible killing
When agent is removed, microorganisms will NOT grow using agent

Germicide/bactericide/bacteriocidal- kills bacteria
Sporicide/ Sporicidal- kills bacterial spores
Fungicide/Fungicidal-kills fungi
Virucide/virucidal-kills viruses

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Static/stasis

Back 253

Growth is halted but when agent removed, microorganisms can grow

Front 254

Sterilization

Back 254

Absolute process
Killing or removal of microorg including bacterial spores
Highest degree of control of microorganisms in that all agents are dead
Material can be dirty or clean but all micoorg dead

*Does not removed bacterial products (LPS)
LPS or endotoxin heat stable and survive autoclave temps but retain endotoxin activity even if bacteria from which it was derived is killed
Pyrogen free: free of biologically relevant levels of endotoxin/LPS and other pyrogens (PAMPS)

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Disinfection

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Killing of many but NOT all organisms
Reduction in # of microorg
For only inanimate objects
Toxic to human tissues

Front 256

High level disinfectant *EXAM

Back 256

Effective against most pathogens but not large # of spores- may be sporicidal over long time

Front 257

Intermediate level disinfectant *EXAM

Back 257

Effective against mycobacteria and other vegetative bacteria, most viruses and fungi
Not really effective against bacterial or fungal spores

Front 258

Low level disinfectant *KNOW

Back 258

Effective against most vegetative bacteria and enveloped viruses and some fungi
Not effective against mycobacteria or spores

Front 259

Sanitization

Back 259

Clean and no pathogens
Does not imply sterilization or complete disinfection
Primarily cleaning with minimal control of microorganisms in that bacteria
Not all bacteria or viruses removed

Front 260

Pasteurization

Back 260

Use of elevated temperature (heat) followed by rapid cooling (to minimize product damage) to kill important pathogens in liquids (milk, egg) but temp below that needed for sterilization
Temp dictated by state laws
Process not sterilized, some bacteria or spores not killed

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Antiseptic

Back 261

Chemicals kill microorg on surface of skin, mucous membrane

Front 262

Asepsis/ aseptic

Back 262

WITHOUT INFECTION
Techniques to prevent entry of infectious agents in human solutions
Treated surface is not sterile or disinfected
Cant sterile SKIN

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Control # of microorganisms

Back 263

1. Material must be sterile
2. Organisms must be excluded from the product
3. Organisms can be present in product but be prevented from reproducing

*May not necessarily kill all agents
It's easy to control microorganisms
More difficult to eliminate them completely from most environments e.g. LPS/endotoxin levels tested in all medical products
e.g. product kills 99.9% bacteria but if bacteria 10^12 then 0.001% of that is ALOT

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Organisms differ in susceptibility to any given agent

Back 264

1. Species of microbe. Vary in resistance to chemical or physical agents
2. Physiological state of microbe. Bacteria in lag or stationary growth phase more difficult to kill
3. Spores highly resistant to same agents that kill metabolically active cells

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Factors affecting killing of microorganisms *EXAM

Back 265

1. Application time varies with agent
2. Takes longer to kill more microorganisms
3. If conc. of agent increased, length of time needed to control microbial agent will decrease. Exceptions:
-It's not always linear relationship e.g. if Phenol diluted to 1/2, length of time to kill increase 64 times
-Alcohol in that case 70% is better at killing than 100%
-Know each agent's methods of action and range of action against various microorganisms
4. For every 10C increase in temp, chemical activity doubles and killing time decrease
5. pH, presence of organic matter and interfering chemicals

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Selecting agent

Back 266

1. Is agent effective against organism in question? Ex: sporocides, tuberculocides, virucides
2. Chlorine used with low organic loads (contamination). Glutaraldehyde unaffected by organic contamination i.e. used with dirty or heavily soiled items
3. Ethylene oxide gas- expensive. Bleach- cheap
4. I2 (inorganic) corrosive and toxic
5. Time must be reasonable
6. Smell, taste, esthetics
7. Item categories
a. critical items- must be sterilized. Those that enter sterile tissue or blood stream e.g. surgical instruments, caridac, urinary catheters
b. Semi-critical items (come in contact with broken skin or mucous membranes) require treatment with disinfectants that have high level of activity. Kill MTB, endospores, vegetative bacteria, endospores e.g. endoscope, thermometers
c. Non-critical items: patient furniture, blood pressure cuff, ECG cleaned with low level disnfectants

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Preservation

Back 267

1. Referigeration
2. Freezing, freeze-drying (lypophilization)
3. Filtration (0.1 microns)
4. Pasteurization (74C, 3-5 sec, rapid cool & at 4C)
5. Mercury salts (themerisol- vaccine or methiolate)

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Antiseptics

Back 268

1. Silver nitrate (heavy metal)
2. Iodine- idophores (providone/ betadyne contain I2)
3. H202
4. Anionic detergents (sodium lauryl sulfate)
5. Alcohol 70%-> 90%
6. Quaternary ammonium compounds. Ex: benzalkonium chloride (Zephiran)

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Disinfection

Back 269

1. Chlorine (bleach)- similar chemicals as I2
2. Phenol
3. Boiling (10 min)
4. Pasteurization
5. Filtration. HIgh efficiency particulate air or HEPA

Front 270

Sterilization

Back 270

1. Incineration/ burning/heat
2. Dry heat/ 180C, 3 hours
3. Autoclave (steam sterlization) 15 lb pressure, 121C, 15 min
4. Ionizing irradiation gamma irradiation (e.g. Cobalt 60, Cessium)
5. UV light irradiation
6. Microwave irradiation (heat method use electromagnetic energy)
7. Ethylene oxide gas
8. Formaldehyde (formalin 27% aqueous soln) liquid or vapor
9. Glutaraldehyde/ o-pthaldelhyde OPA liquid
10. B-propiolactone
11. Peractic acid liquid
12. H202 gas

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Barrier techniques

Back 271

1. Hand washing: MOST EFFECTIVE means of preventing infection spread. Soap with chlorohexidine. Alcohol based cleaners avoid skin dehydration. Wash before and after caring for patient if even if gloves worn
2. Gloves- after each patient, contaminated, clean area- catheter
3. Gowns- disposed of
4. Masks, glasses, face shield- care for patients under stringent types of isolation
5. Personal hygiene
6. Physician equipment- stethoscope with ethanol wipe or disinfectant
7. 100% compliance with infection control measures- fully expected in hospitals

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Chemotherapeutic agent

Back 272

A drug used to treat any illness or diseases
With infectious disease, refer to antibiotics

Front 273

Antimicrobial agent

Back 273

Interferes with proliferation of microorganisms (viruses, bacteria, protozoan, fungi)

Front 274

Antibiotic

Back 274

Compound with antimicrobial activity whose source is natural living organisms, often soil microorganisms

Front 275

Static- Bacteriastatic

Back 275

Antimicrobial agent that INHIBIT GROWTH when present but doesn't kill
Effect reversible
Rely on functional immune system
Slowing growth of pathogen, slows disease progression
Allows immune system to do its job, eliminate pathogen
If immune system doesn't function, infectious agent grow again when antimicrobial agent removed

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Cidal

Back 276

Agents KILL
Irreversible lethal effect
Killing not same as getting rid of eliminating dead cell/viruses reminants remain
Bacterial cidal agents needed in patients with neutropenia or other immune deficiencies

Front 277

Narrow spectrum antibiotics *EXAM

Back 277

Affect only certain classes of microorganisms
e.g. antibiotic that is efficacious against gram + bacteria or one that is effective against gram - bacteria or specific group of bacteria
Preferential targeting is preferable; WANT

Front 278

Broad Spectrum Antibiotics

Back 278

Efficaous against gram + AND gram - bacteria
Not preferable because they kill normal flora
Result in secondary or superinfections
Preferable if:
- empiric therapy needed for life threatening infection until agent defined
- prophylaxis (prevention) to certain procedures

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Resistant

Back 279

Microorganisms that are NOT inhibited by clinically achievable concentration of chemotherapeutic agents

Front 280

Sensitive

Back 280

Microorganisms that ARE inhibited by clinically achievable concentration of chemotherapeutic agents

Front 281

Antimicrobial sensitivity determination

Back 281

In vitro antimicrobial susceptibility test: performed on patient isolates to determine what antibiotics should be effective in treating a patients infection

Front 282

Kirby Bauer Disc Diffusion Assay (qualitative)

Back 282

Standardized agar diffusion method is qualitative measure in vitro antibiotic susceptibility
Qualitative results expressed as sensitive (s), intermediate resistance (IR) or resistant (R)
Measures capacity of antibiotic to inhibit growth but this test cant distinguish between static or cidal
Methodology:
1. Uses filter paper discs impregnanted with antibiotic to be tested
2. Standardized lawn of patients bacterial ioslate to be tested is placed on surface of agar
3. Antibiotics impregnanted in each disc diffuse out into agar
4. Size of zone of inhibition is dependent upon many factors
5. Diameter of zone of growth inhibition surrounding each disc is compared to determine if organism tested is sensitive (GROWTH INHIBITED) or resistant (GROWTH NOT INHIBITED) to that antibiotic
6. Standard disc concentrations used based on achievable serum drug levels when standard package insert dosages administrated and depend on whether PO, IV, IM, administrations used

Front 283

Minimum Inhibitory Concentration (MIC) (quantitate)

Back 283

In vitro antimicrobial susceptibility test that generates quantitate measure (ug/ml) of antibiotic susceptibility
Amount of antibiotic required to inhibit growth (either static or cidal) but this test cant distinguish between two

MIC < MBC

Front 284

Minimum Bactericidal Concentration (MBC) (quantitative)

Back 284

In vitro antimicrobial susceptibility test that generates quantitate measure (ug/ml) of antibiotic susceptibility
Required to kill (bactericidal) 99.9% of patients bacterial isolate, not 100% of isolate. 99.9% killed.
MIC always < MBC
Result in antibiotic concentration that exceeds the MBC at site of infection
Endocartitis, bacterial meningitis, & osteomyelitis determine MBC and exceed MBC if pharmacological possible
Treatment/clinical dosages adminstered should result in antibiotic conc that exceeds the MBC at site of infection
For endocartitis, bacterial menin, osteomyelitis need to determine MBC and then exceed the MBC if possible

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Antimicrobial serumcidal concentration

Back 285

In vitro, quantitate antimicrobial susceptibility test
Minimum conc of antimicrobial agent required to kill patients bacterial isolate in presence of patients serum
Serum content complex and variable from pt to pt
Determine if target level of antibiotic are being achieved in vivo
Anything in pt blood that will enhance kill so can use less antimicrobial agent

Front 286

Antibiotic resistance trends/ antibiogram

Back 286

Published record of a hospital's antimicrobial resistance and susceptibility patterns among clinical isolates and its most prescribed antibiotics
Hospital have own flora
Allow for rational use of antibiotic
Restrict antibiotics that bacteria resistant to

Front 287

Effective antimicrobial chemotherapeutic agents

Back 287

1. Achieve inhibitory or bactericidal activity at site of infection without toxicity to host
2. Selective toxicity: all agents have some toxicity
- Poor selective: drug target is to the same target in human host. Harmful to patient and microbe
-Good selective: Less similar target in human host. Well tolerated by pt but harmful to microbe
3. Good pharmacokinetics
-penetration, persistence, accumulation, half life, activity in target tissues
4. Host's immune system not affected
5. Pathogens not easily acquire resistance to agent selected
6. Agent poorly immunogenic (low antigenicity & allergy)
7. Baceriocidal drug
8. Cost efficient

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Limitation to effective chemotherapy *EXAM

Back 288

1. Abscess formation- areas of low O2 levels and blood flow or perfusion -> tissue necrosis
2. Drug, immune cells, abs unable to penetrate abscess
3. Infectious agent multiplies slowly, minimize effectiveness of drugs which depend on neosynthesis of cell wall/peptidoglycan to work
4. Phagocytes in purulent lesions are dead. New WBC and abs cant reach site. By products of anaerobes inhibit neutrophil migration into tissue
5. Abs present at low levels due to poor access
6. Tissue breakdown products decrease effectiveness of sulfonamides (inhibitors of folic acid synthesis in bacteria) under abscess conditions due to exogenous folic acid that microorganisms will take up
7. Effectiveness of aminoglycosides depressed from low pH and binding of agent under anaerobic ways to NA
8. Effective treatment requires drainage and removal of necrotic tissue

Front 289

Limitation to effective chemotherapy *EXAM

Back 289

Foreign bodies (splinters/bullets/shrapnel/catheters): biofilms form on indwelling catheters
prostheses shelter microorganisms
Allow for more rapid growth of agent (bacteria persist in biofilms)
Remove catheter if infected
REMOVE foreign bodies

Front 290

Limitation to effective chemotherapy *EXAM

Back 290

Infectious diseases are major cause of death in immunocompromised hosts
Antimicrobials work best with intact immune system

Front 291

Limitation to effective chemotherapy *EXAM

Back 291

Treat one disease and new diff disease develops at another site from overgrowth of normal flora that are normally supressed by other normal flora
Examples: treatment of pharyngitis leads to
-treat of pharyngitis-> vaginal yeast infections
-treat pneumonia -> Clostridium difficle antibiotic associated pseudomembranous colitis

Pt colonized by being in hospital, give antibiotic wipe out normal flora and clostridium difficile grow

Front 292

Limitation to effective chemotherapy *EXAM

Back 292

Different antibiotics penetrate diff tissues
Penetration and accumulation of drugs at appropriate site is both tissue and drug dependent. Dont penetrate blood brain barriers

Antimicrobial drug interactions do occur

Front 293

Justified chemoprophylaxis

Back 293

1. Crede procedure: AgNO3 and erythromycin/ tetracycline eye drops or salve to prevent opthalmia neonatorum
2. Prophylaxis against malaria
3. Rheumatic heart disease patients to prevent group A streptoccocal disease
4. Prophylaxis against bacterial endocariditis- dental manipulations, respiratory + GI procedures
5. Pts undergo surgeries that cross mucosal surface that contain normal flora e.g. Bowel surgery thats contaminated with bacteria
6. Immunocompromised patients
7. Reccurent UTI
8. Animal and human bit wounds
9. Post exposure prophylaxis:
-meningococcal meningitis disease outbreaks
-persons with MTB infection or exposed to TB
-HIV: exposed to or infected with
-6 feet or 2 meters close contact for person with airborne pathogen

Front 294

Unjustified chemoprophylaxis *EXAM

Back 294

1. Prevent secondary bacterial pneumonia in influenzae or other viral resp infections
2. Clean surgery: general, skin lesion removal, orthopedics, plastic
3. Because pt insists on antibiotic

Front 295

5 chemotherapeutic agents

Back 295

1. Metabolic analogs
2. Cell wall active agents
3. Agents which affect membrane integrity
4. Agents which affect nucleic acid synthesis
5. Protein synthesis inhibitors

Front 296

Metabolic Analog: Antibacterial

Back 296

Mode of action: Inhibit FA and cell wall synthesis
Synthesis of nucleotides-> Inhibition of NA (RNA and DNA) & protein synthesis
Drugs: Isoniazid, Sulfa drugs (TMP-SMX= co-trimazole, bactrim, septra)

Front 297

Inhibition of cell wall synthesis: Antibacterial

Back 297

Drugs:
1.Pencillins
2. Cephalosporins
3. Cabapenems
4. Monobactams
5. Bacitracin- topical use only
6. Vancomycin
7. Cycloserine

Front 298

Inhibition of Protein Synthesis: Antibacterial

Back 298

Drugs:
1. Chloramphenicol 2. Streptogramins
3. Aminoglycosides: NOT effective against intracell bacteria
4. Tetracyclines
5. Oxazolidinones
6. Glycyclines
7. Macrolides
8. Mupiricin- topically to prevent nasal carriage by S. aureus

*Drugs require bacteria growing rapidly to be effective

Front 299

Nucleic acid: Antibacterial

Back 299

Inhibition of DNA packaging via DNA gyrase/topoisomerase (unwind DNA)
Drugs:
1. Sulfonamides, trimethoprim
2. Fluroquinolones / quinolones
3. Rifampin
4. Metronidazole- anaerobic infectious agents

Front 300

Alteration of cell membrane function: Antibacterial

Back 300

Drugs
1. Polymyxin : poor selective toxicity
2. Bacitracin

*Topical only

Front 301

Metabolic Analog: Antifungal

*Fungi- Eukaryotes so selective toxicity bc we eukaryotes too

Back 301

Inhibits DNA/RNA and protein synthesis
Drugs:
1. 5- Flurocyotosine

Front 302

Inhibition of cell wall synthesis: Antifungal

Back 302

Drugs:
1. Ecinocandins
2. Pneumocandins
3. Caspofungin acetate

Front 303

Inhibition of protein synthesis: Antifungal

Back 303

NONE

Front 304

Inhibition of nucleic acid synthesis: Antifungal

Back 304

Drugs:
1. 5- fluorocytosine

Front 305

Inhibition of cell mitosis (cell division): Antifungal

Back 305

Drugs:
1. Griesfulvin

Front 306

Inhibition of fungal sterol synthesis -> alteration of cell membrane structure/function

Back 306

Drugs:
1. Polyenes (Amphotericin B)- B worst selective toxicity bc target membrane, most serious, damage kidney
2. Imidazoles/Azoles
3. Triazoles
4. Morpholines
5. Allyalmines/Thicarbamates

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Synergism

Back 307

2 drugs when used in combination are cidal at concentrations lower than that of either component drug used separately e.g. 1+1 =32
Has beneficial effect of administering lesser amounts of toxic drug e.g. Aminoglycoside and penicillin

Front 308

Additive

Back 308

Limited form of synergy with limited clinical usefulness
e.g. 1+1 =2
When 1 or 2 drugs are toxic, then decreasing concentration of each by 50% is beneficial

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Antagonism

Back 309

Reduction in activity of one or both components when both present e.g. 1+1 = 0.5
Antagonism due to:
-Competition for binding site- erythromycin and chloramphenicol
-Drug/drug interaction- opposing effects tetracycline and penicillin. Protein synthesis inhibitor such as tetracycline could slow growth of bacterium and production of peptidoglycan, reducing target availability for penicillin

Front 310

Indifference

Back 310

Combined action is same as with either component
ie. some antibiotic combinations are indifferent
e.g. 1+1 =1
Not clinically useful

Front 311

Combination Chemotherapy

Back 311

Polymicrobic infection both aerobes and anaerobes
Enhance antibacterial activity (synergism) to use lower doses of toxic drug and increase cidal activity
Treat life threatening infection
Prevent emergence of resistance e.g TB , HIV

Front 312

Mechanisms of Resistance to Antimicrobial agents

Back 312

Alteration of drug target- modification of target site:
1. Altered penicillin binding proteins -> reduce sensitivity to penicillin
2. Altered DNA gyrase -> reduce sensitivity to fluroquinolones
3. Expression of dihydrofloate reductase -> reduce trimethoprim sensitivity
4. Replacement of D- alanine with lactic acid in murein side chain -> vancomycin resistance

Front 313

Prevent access of drug to target:

Back 313

1. Drug efflux pump- more drug excreted than enters cell
2. Reduced drug permeability: changes in cell reduce rate at which drug enter

Front 314

Inactivation of drug *EXAM

Back 314

Destruction of agent e.g. penicillin is substrate for B-lactamase
1. Organisms elaborate B lactamase which cleave the B- lactam ring of B-lactam ring containing antibiotics. Discovery of compounds resistant to beta lactamase or capable of inactivating them through mutations that inactivate these antibiotics. 900 enzymes discovered. Some chromosomally mediated, majority on transmissible genetic elements
2. B lactamase inhibitors are drugs developed to inhibit B-lactamse
3. 4 major classes of resistance mechanisms involving hydrolysis of drug to B lactam antibiotics
a. Penicllinases
b. Cephalosporinases (AKA AmpC-Type)
c. Extended spectrum B-lactamsases (ESBLS)
d. Carbapenemases
* c+d moving to forefront

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ESBL

Back 315

Hydrolyze/resistant to Blactam ring containing antibiotics
Infections caused by ESBL-producing organisms resulted in poor outcomes, reduced rates of clinical and biological response, longer hospital stay, and greater hospital expense

Front 316

Carbapenems (imipenem and meropenem)

Back 316

Last line of defesnse against invasive or serious infections
Treat life threatening infections caused by gram -, drug resistant pathogens (extended spectrum B lactamase-producing enterobacteria)

Front 317

Metallo-beta-lactamse-carbapenemase

Back 317

Carbapenem-resistant Enterobacteriacea (CRE) via production of :
Note: carbapenem hydrolyzing B lactamase gene designated bla
1. Class A- Klebsiella pneumonia carbapenamase
KPC producing Enterobacteriacea widespread in US and most common mecahsnism of carbapenem resistance among Enterobacteriaceae
2. Class B- metallo beta lactamase (MBL) carbapenemase include:
i. Verona integron encoded metallo beta lactamase (VIM)
ii. New Dehli metallo beta lactamase (NDM-1)
iii. IMF type
MBL have widest substrate spectrum
3. Class D- oxacillinases (OXA) type carbapenemase found in nonfermenting bacteria except for OXA 48 which is found in only enterobacteria

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Resistance determinants detected by

Back 318

Modified HOdge test or by PCR
1. Screen test
2. Confirmatory test

Front 319

Tolerance

Back 319

Evasion of killing
NO change in MIC but MBC is high
Studies are resistricted to B lactam antibiotics and cell wall active agents
1. Phenotypic- evasion of killing by depression of bacterial growth rate
2. Genotypic- depression production of murein (peptidoglycan ) hydrolases

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Epidemiology

Back 320

Study of occurrence, spread and control of disease in population
Basic science and most fundamental practice of public health and preventive medicine

Front 321

Incidence

Back 321

Number of new cases (reported/diagnosed) in population

Incidence rate- number of new cases (reported) in population in specified time period: PERSON TIME

How rapidly a disease is developing in population
Calculation of IR is time dependent

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Incidence Rate used to determine:

Back 322

1. Frequency- # of new occurrences of disease, injury, death, birth in study population; alive to death
2. Mortality rate- # of deaths in pop over time
3. Attack rate- # of ppl who develop illness vs. # exposed to agent during disease outbreaks
4. Secondary attack rate- # of persons who develop illness from first person who became ill (primary or index case)
5. Risk- probability of developing disease at time- rate. Incidence increase, probability of getting disease increase
Risk is cumulative measure of incidence, occurrence of new cases, proportion of uninfected individuals who will contact infection over time
6. Birth rate

Front 323

Prevalence or point prevalence

Back 323

New and old cases
Whether to order test or how to treat
Snapshot of whole picture- a RATIO
Seroprevalance- # of people who are antibody +/ DTH positive for agent

Front 324

Time-space clustering

Back 324

Occurrence of specific disease in human population (space) over time

Front 325

Seasonality

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Incidence of disease consistently higher during specified time of year so risk of developing disease increases during time ex: influenza in winter

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Morbidity

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Diseased state or ratio of sick to well in population

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Sporadic *EXAM

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Diseased state or ratio of sick to well in population

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Endemic *EXAM

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Disease rate
Disease of humans present in region at constant level

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Epidemic *EXAM

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Increase endemic
Increase in incidence of disease (above expected incidence/endemic rate) in population in region
Epidemic only in presence of endemic rate

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Pandemic

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Epidemics in large portion (worldwide)

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Zoonosis

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Disease of animals transmissible directly to humans (rabies)

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Enzootic

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Disease of animals at constant rate
Rate of endemic disease in animal

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Epizootic

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Sudden increase in incidence of particular disease in animal population in region

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Contagious *EXAM

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Diseases communicable or transmissible by contact with sick humans or their fresh secretion or excretions, NOT zoonosis, NOT insect vectors, NOT via inhalation/ingestion of soil or water infections

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Carrier

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Person or animal who contains, spreads, or harbor infectious agent (inapparent carrier, immune carrier, transient carrier

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Communicability (transmissibility)

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Measure of pathogen's capacity to spread of disease in population

Degree of communicability vary high to low
Short (hours) or long incubation period (week

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Non-communicable infectious disease

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1. Normal flora as source of infection in organs/tissues (e.g. perforated bowel)
2. Performed microbial toxins as source (food borne microbial intoxications or food poision)
3. Environmental pathogens (tetanus)
4. Zoonoses= humans receptive but dead end host

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Period of communicability

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Time during which person considered contagious
During course of infection-diease, stage or stages that an infected person is contagious, relates to potential spread of Dx through population
Period of communicability occurs during a. incubation period b. disease c. convalescence, chronically

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Carriers

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Individuals capable of infecting other individuals
Types of carriageL
1. Inapparent- no sign or symptom. Most dangerous control
2. Casual or transient
3. Chronic or long term (convalescent) after disease

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Incubation period

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1. Time period between diagnosis of index case and development of signs and symptoms in patients contacts
2. Time period after entry of agent into host and ending with initiation of disease

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Treatment of incubation

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Long incubation period allows for post-exposure prophylaxis with 1 or more:
a. antibiotics
b. IG
c. vaccination: active immunization after exposure to infectious disease should be done to prevent that disease if incubation period of disease exceeds time required to produce immunity (7-> 14d required for primary immune response)
Human host doesnt mount immune response to infecting agent during incubation period

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Epidemiological studies

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1. Nature of infective agent
2. Its source and mode of transmission
3. Determine conditions that favor or control dissemination of infection

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Epidemiological triad

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In order for disease to occur, harmful agent comes into contact with susceptible host in proper environment

HOST ENVIRONMENT AGENT
PERSON PLACE TIME

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Herd immunity

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Resistance of group of individuals to infection and spread of infectious agent based on susceptible and immune individuals in group
Epidemics of disease occur when proportion of susceptible disease if high or disappear as proportion of immune individuals increase
100% immunity not required to halt epidemic
Doesnt matter what resistance of agent is
Determine level of herd immunity to prevent disease:
-disease spread by airborne (flu) route require higher proportion of immune individuals than disease by direct contact (STD)
-communicability
-attack rate

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Presence of vector (if required for transmission)

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Malaria does not occur in nepal bc mosquitoes that transmit malaria cant fly high
Mechanical vector- physically transport agent and doesnt serve as agents host ex: GI more in summer bc flies land on feces then food
Biological vecotr- ticks, vector in which agent replicates

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Infection

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Invasion of host by infectious agent which multiply in close association with host tissue
Can have infection w/o getting disease

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Disease

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Morbid process that doesnt necessarily involve infection
1. Noninfectious disease include cancer, heart attack
2. Infectious disease- signs and symptoms caused directly or indirectly by infectious agent

*Infection: HIV, MTB, Mycobacterium tuberculosis
*Disease: AIDS, TB

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Spectrum of - infectious disease- disease spectrum

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Tip of iceberg/ eyes of hippopotamus
Death
Infected with symp
Infected with no symp
Not infected

Susceptible people exposed to biologic agent certain portion will:
a. no clinical or laboratory evidence of infection
b. no clinical evidence of infectious disease
c. continue normal activity but can spread disease
d. develop mild to severe clinical illness
e. die from disease

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Spectrum of infection/ types of infections

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1. Inapparent (subclinical)- seroconversion with no detectable clinical symptoms. Individual sometimes capable of spreading agent. Most common outcome of viral infection *can take blood test
2. Primary- clinically apparent invasion and multiplication of microbes in body tissues causing local tissue injury
3. Secondary- microbial invasion subsequent to primary infection (influenza)
4. Superinfection- microbial infections which occur at site other than primary site and after treatment of primary infection
5. Mixed- 2 or more microbes infecting same tissue. Common. Treatment required
6. Co-infection- infections with 2 distinct agents simultaneously
*some infectious disease have multiple etiology. More than one agent can cause same disease but in patient only ONE agent present- not mixed infection or co-infection. Pneuomniae caused by separate infections: bacteria, virus, fungi, protozoa, helminth
7. Acute rapid progression (hours or days) and brief duration. Subacute- less rapid progression, more prolonged duration
8. Fulminant- infections that occur suddenly and rapidly progress
9. Chronic- prolonged duration (week month or years)
10. Dormant (latent) carrier state
11. Localized- confined to small area or to organ
12. Generalized- diseeminated to many body regions
13. Pyogenic- pus forming
14. Retrograde- microbes ascend in duct or tube against flow of secretions or excretions

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Spectrum of infection/Types

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1. Acute- rapid onset (hours or days) brief duration (days or weeks)
2. Subacute (less rapid onset, less severe symptoms)
3. Fulminant- occur suddenly and intensely
4. Chronic- prolonged duration (weeks months or years)

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Pathogens

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Ability of agent to cause disease

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Frank pathogen

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Organism which cause disease in normal host, when identified in clinical specimens probable agent of disease
Cause disease at particular site

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Opportunistic pathogen

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Etiologic agent isolated from patient whose host defense mechanism compromised

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Nonpathogen

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Not seen in human disease

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Pathogenecity

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Capacity or ability to cause disease

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Virulence

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Degree to which agent cause disease
Measure of pathogenicity:
1. Degree of virulence ranges from low to high. Related to directly to ability of organism to cause disease despite host defense.
2. Quantitated in animals or humans. Expressed as numbers of infectious agent that will infect or kill 50% of inoculated susceptible animals
a. Determine LD50 (Shigella) and ID50 (Salmonella) for comparison of disease agents with capacity to cause disease
b. Degree of pathogenciity and dose are related. If highly virulent, fewer organisms will required to cause disease (Lower ID50)

Virulence factors enable pathogen to cause disease

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Invasiveness

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1. Pathogen invade and replicate in host tissues/cells
2. Characteristic of pathogen conferred by virulence factors encoded by pathogen
3. Bacterial pathogens groups according to invasiveness and life cycle
a. Extracell bacteria are non invasive eg. Corynebacterium diptheriea
b. Facultative intracellular bacteria replicate outside of host cells or replicate inside host e.g. Mycobacterium tuberculosis
*c. Obligate intracellular bacteria ONLY live intracellulary e.g. Chylmydia spp, Ricksettsia spp, Coxiella spp.

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Horizontal modes of transmission

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1. Aerosol- most difficult to control/ prevent; easiest transmission mode
2. Ingestion- 2nd easiest transmission mode

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Vertical mode

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Mother to child -transplacental/perinatal