Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
407 Cards in this Set
- Front
- Back
|
2 types of acellular pathogens:
|
1. viruses
2. prions |
|
|
viruses are made up of:
(2) |
1. nucleic acids (DNA OR RNA)
2. protein coat |
|
|
prions are:
|
potein particles that cause disease
- NO nucleaic acids, only proteins |
|
|
neither viruses nor prions can grow without:
|
a host
|
|
|
the major differences between prok's and euk's are:
(2) |
1. nucleus
2. visible organelle |
|
|
the vast majority of euk's are:
|
microorganisms
|
|
|
lots of euk's are actually single-celled, and some prok's are:
|
multi-celled
|
|
|
there are NO archaea that cause:
|
human disease
|
|
|
2 characteristics that are unique to bacteria:
|
1. 70S ribosome
2. peptidoglycan cell wall |
|
|
what's the significance of bacteria possessing unique characteristics?
|
they can be targeted to defeat bacteria
|
|
|
bact. and archaea are BOTH:
|
prok's
|
|
|
6 types of human pathogen:
|
1. viruses
2. prions 3. bact. 4. fungi 5. protazoa 6. helminths (worms) |
|
|
protozoa are uni-
|
cellular
|
|
|
fungi, protozoa, and helminths are all:
|
euk's with mit.
|
|
|
bact, fungi, protozoa, and worms all carry:
|
BOTH DNA and RNA
|
|
|
bacteriophage =
|
virus that infects prok's
(bact. and archaea) |
|
|
bacteriophage cycle:
(6) |
1. Attachment to host
2. Penetration 3. Uncoating 4. Synthesis of viral components 5. Assembly of new viruses 6. Egress/release of new viruses |
|
|
"Uncoating" of bacteriophage refers to:
|
**injecting nucleic acid into the host, while the coat stays outside**
|
|
|
b/c of prok. cell, wall, bacteriophages have to egress by:
|
degrading the cell wall and lysing the host cell
|
|
|
phage are 10x more common in nature than:
|
bact.
|
|
|
phages are used to eliminate:
|
pathogenic bact. during food processing
|
|
|
lytic growth pattern of a virus =
|
normal reproduction cycle ending with lysis of host cell
|
|
|
4 steps of lysogenic growth:
|
1. phage DNA inserts itself into bact. chromosome
2. lies dormant 3. host division results in multiple copies of viral DNA within multiple cells 4. with the right signal from the environment, cell goes into lytic cycle => production/release of new viruses, lysis of host cell |
|
|
prophage =
|
genetic material of bacteriophage that has inserted itself into a bacterial chromosome
|
|
|
lysogenic conversion =
|
the endowment of toxic / disease-causing properties by a viral infection to a bacterial host
|
|
|
vertical gene transfer ~~
|
parent to progeny
|
|
|
horizontal gene transfer =
|
obtaining DNA from other organisms
|
|
|
horizontal gene transfer increases the risk of:
|
pathogens developing resistance or disease-causing properties
|
|
|
horizontal gene transfer is also called:
|
Lateral transfer
|
|
|
3 types of horizontal transfer:
|
1. Transduction
2. Transformation 3. Conjugation |
|
|
gene transduction comes in 2 forms:
|
generalized
specialized |
|
|
generalized gene transduction =
|
bact. DNA trasnferred to a different bact. b/c a virus accidentally incorporated the original host's DNA into its copies
- ANY of the host's DNA can be incorporated in this way |
|
|
specialized gene transduction differs from generalized in this way:
|
the bact. DNA incorporated into the viruses is only ever the DNA from NEAR the prophage
|
|
|
gene transformation =
|
uptake of naked, extracellular DNA
|
|
|
which bacteria participate in transformation?
|
only those who have the necessary ingredients.
in other words, it's a rare mechanism |
|
|
3 steps of gram positive transformation:
|
1. binding of DNA to bact. surface
2. fragmentation (strand breaks in half) 3. transport of one of those strands into the cytoplasm |
|
|
3 steps of gram negative transformation:
|
1. binding/fragmentation
2. entry into the periplasm (as double strand) 3. entry into the cytoplasm (as single strand) |
|
|
conjugation =
|
transfer of genetic info via direct cell-to-cell contact
|
|
|
conjugation:
(2) |
1. unidirectional
2. conservative |
|
|
what does it mean for conjugation to be conservative?
|
the DNA being transferred is *replicated*
- the donor retains the original DNA - a complementary strand is synthesized by the recipient |
|
|
special feature of gram negative bact.' conjugation =
|
pilus to contact the other cell
|
|
|
plasmid =
|
extrachromosomal pieces of DNA within bacteria
|
|
|
plasmids are *nonessential*, but useful for:
|
allowing bact. to grow in diverse environments
|
|
|
plasmids carry genes for:
|
antibiotic resistance, toxins, etc.
|
|
|
plasmids replicate ________________ of chromosomes
|
independently
|
|
|
recombination =
|
incorporating DNA into host chromosome
|
|
|
3 types of recombination:
|
1. homologous
2. site-specific 3. non-homologous/illegitimate |
|
|
homologous recombination =
|
pairing of *similar* DNA sequences
|
|
|
site-specific recombinaiton =
|
combination of **short**, **specific** sequences
|
|
|
non-homologous recombination does NOT require:
|
sequence homology
think transposons |
|
|
transposable gene elements are also called:
(3) |
transposons, jumping genes, and selfish genes
|
|
|
transposons insert themselves at:
|
random locations of the genome
|
|
|
potential consequences of transposon insertion:
(3) |
1. expression of genes (e.g. antib. resistance)
2. interruption of gene expression 3. alteration of expression of neighboring genes |
|
|
2 types of transposons:
|
1. insertion sequences
2. composite transposons |
|
|
insertion sequences =
|
2 inverted repeat sequences flanking a gene that encodes transposase
- the simplest kind of transposon |
|
|
transposons are found in both:
|
prok's AND euk's
|
|
|
composite transposons come in 2 flavors:
|
non-replicative
and replicative |
|
|
with replicative composite transposons, both the donor and the recipient have:
|
the transposon sequence at the end of the process
|
|
|
genomic islands =
|
groups of **foreign** genes that encode related functions
|
|
|
20-30% of bact. genomes is:
|
of foreign origin
|
|
|
pathogenicity islands encode:
(5) |
1. secretion mlcls
2. adhesion mlcls 3. invasion of euk. cells 4. toxins 5. siderophores etc. |
|
|
bact. genomes are DYNAMIC; DNA is constantly being:
|
rearranged, deleted, mutated, duplicated
|
|
|
viral genomes are also:
|
dynamic
|
|
|
1 gene = 1 ____________ in length
|
kilobase
|
|
|
surface of bacteria ~~
|
protection, communication, and lots of other things
|
|
|
cell walls allow bacteria to withstand:
|
their high internal osmotic pressure
|
|
|
sphere-shaped bacteira are called:
|
cocci
|
|
|
rod-shaped bacteira are called:
|
bacilli
|
|
|
curved rod-shaped bacteira are called:
|
vibrios
|
|
|
spiral-shaped bacteira are called:
|
spirochetes
|
|
|
multi-shaped bacteira are called:
|
pleomorphs
|
|
|
the cell wall is made up of:
|
peptidoglycan
|
|
|
peptidoglycan is also called:
|
meurin
|
|
|
***peptidoglycan cell walls are unique to:***
|
**unique** to bacteria
|
|
|
peptidoglycan =
|
sugar backbones linked by short peptides
|
|
|
cell walls are found in ALL bact. **except**
|
mycoplasma
=> unique target |
|
|
cell walls are NOT found in:
|
euk's and archaea,
|
|
|
what's one enzyme that degrades cell walls?
|
lysozyme
|
|
|
4 steps of the gram staining procedure:
|
1. add crystal violet (blue dye)
2. dry with iodine 3. wash with ehtanol (organic solvent) 4. counter-stain with red dye (safrin) |
|
|
gram staining reflects:
|
differences in the cell wall
|
|
|
gram positive bacteria stain:
|
blue/purple after organic solvent
|
|
|
gram negative bact. become clear after organic solvent and stain:
|
red
|
|
|
gram stains don't work for:
(4) |
1. myobact
2. mycobact 3. obligate intracellular 4. spirochetes |
|
|
why don't gram stains work for mycobacteria?
|
they have no cell walls
|
|
|
why don't gram stains work for spirochetes ?
|
too thin for light field microscopy
- need dark field |
|
|
3 unique features of gram positive structure:
|
1. really thick cell wall
2. teichoic/teichuronic acid 3. lipoteichoic acid |
|
|
teichoic acid is attached to:
|
the sugar backbone of meurin
|
|
|
teichoic acid becomes teichuronic acid when:
|
the bact. doesn't have Phosphate
|
|
|
lipoteichoic acid is attached to:
|
plasma membrane
(aka cytoplasmic membrane aka cytoplasm) |
|
|
what causes rigidity in gram positive cell walls?
|
negative charges of all those acids
|
|
|
unique features of gram negative bact:
(3) |
1. really thin cell wall
2. TWO plasma membranes 3. LPS |
|
|
the periplasm (aka periplasmic space) of gram negative is found between:
|
the cell wall and the inner membrane
|
|
|
***the outer leaflet of the outer membrane of gram negative bact is called:***
|
lipopolysaccharide (LPS)
|
|
|
structure of LPS =
|
Lipid A - core polysaccharide - repeating O antigen
|
|
|
Lipid A:
(2) |
1. attaches to inner leaflet of outer membrane
2. a classic **endotoxin** |
|
|
endotoxins are NOT:
|
secreted
|
|
|
the extra membrane of GN's makes them more:
|
resilient to antibiotics
- harder to get stuff in |
|
|
the plasma membrane is composed of lipids, so it's a barrier to:
|
hydrophilics
|
|
|
the thick cell wall of GP bact is composed of:
|
sugars and AA's
|
|
|
sugars and AA's hydro*philic*, so they are a barrier to:
|
hydrophobics
- GN walls are the same |
|
|
4 layers of bact.:
|
1. S-layer
2. Capsule OR Slime layer 3. Pili/Fimbrae 4. Flagella |
|
|
the S-layer is made of:
|
glycoproteins
|
|
|
the S-layer protects against:
(2) |
Complement and phag.
|
|
|
the capsule is made of:
|
polysaccharides
- protects against phag. |
|
|
the Slime layer is made up of:
|
polysaccharides
|
|
|
the Slime layer is also called:
(2) |
glycocalyx or exopolysaccharide matrix
|
|
|
the Slime layer of bact. mediates:
|
attachment
|
|
|
the pili/fimbrae function in:
(2) |
1. attachment
2. movement - found in both GP and GN bact. |
|
|
flagella ~~
|
locomotion
|
|
|
"antigenic variations" means:
|
different bact. have different surface antigens
|
|
|
what kind of antigens do flagella provide?
|
H antigens
|
|
|
what kind of antigens do capsules provide?
|
K antigens
|
|
|
what kind of antigens do the outermost parts of LPS' provide?
|
O antigens
|
|
|
teichoic/teichuronic acids are also:
|
*antigens*
|
|
|
antigenic variation =>
|
minority of bact. escaping the the host's AB's
=> become majority population => some of this new minority express different antigens => cycle repeats (~recurrent fevers) |
|
|
flagella are _____ longer than the cell
|
10x
|
|
|
lipoproteins of GN's connect:
|
the cell wall to the outermembrane
|
|
|
LPS is uniqe to:
|
GN bact.
|
|
|
teichoic acid is unique to:
|
GP bact.
|
|
|
bact reproduce via:
|
binary fission
one cell becomes two, two become four, etc. |
|
|
if bact. replicate and stick together, they are called:
|
diplo
|
|
|
chains of divided bact. are called:
|
strepto
|
|
|
four divided bact. in a square are called:
|
a tetrad
|
|
|
8 divided bact. arranged in a cube are called:
|
sarcina
|
|
|
irregular formations of divided bact. =
|
*staphylo* bact.
|
|
|
binary fission => _______________ growth
|
exponential
|
|
|
**small size of bact. => **
|
**rapid** growth
|
|
|
exponential growth + short generation time =>
|
explosive growth
|
|
|
one response of bact. to environmental pressures =
|
**make endospores**
|
|
|
endospores =
|
dormant bacteria that are resistant to heat, radiation, antibiotics, etc.
- can re-enter growth when it's beneficial to them |
|
|
3 best examples of spore-forming bact:
|
1. Basillus anthracis
2. Clostridium botullinum 3. Clostridium tetanus |
|
|
**bact. require iron; they fight for the host's iron by synthesizing:**
|
**siderophores**
|
|
|
siderophores =
|
mlcls that remove iron from the host's proteins
|
|
|
"troph" ~~
|
feeding/food
|
|
|
bact are classified by what their energy source is:
(2) |
1. light => phototrophs
2. redox rxns => chemotrophs |
|
|
bact. are classified by their electron donor source:
(2) |
1. inorganic cmpds => lithotrophs
2. organic cmpds => organotrophs |
|
|
bact. are classified based on their source of carbon:
(2) |
1. CO2 => autotrophs
2. organic cmpds => heterotrophs |
|
|
**all human pathogenic bact. are:**
|
chemo-organo-heterotrophs
|
|
|
*oxidation is often a loss of:*
|
H atom
=> H+ and electron |
|
|
electrons move from:
|
a LOW redox potential to a high redox potential
|
|
|
negative E (redox potential) means:
|
it HATES having electrons
|
|
|
energy is released in the process of:
|
transferring electrons
|
|
|
the final electron acceptor in fermentation is:
|
organic
|
|
|
the final electron acceptor in respiration is:
|
inorganic
|
|
|
in fermentation , the oxidation state of the electron donor (substrate) has:
|
NO NET change
- in respiration, there IS a net change |
|
|
in fermentation, the energy yield is:
|
low
(it's high in respiration) |
|
|
3 examples of products produced by fermentation:
|
acids
alcohols gases |
|
|
2 mechanisms of ATP synthesis:
|
1. substrate-level P'n
2. ox. P'n |
|
|
substrate-level P'n =
|
P transferred from NAD+ to substrate to ADP
|
|
|
ox. P'n =
|
electron shuttled across ETC, creating an H+ gradient
=> ATP synthase uses energy of gradient to add P to ADP |
|
|
ox. P is MUCH more ______________ than substrate-level P'n
|
efficient
|
|
|
**O2 LOVES:**
|
electrons
|
|
|
O2 takes electrons and forms:
(2) |
1. superoxide (negative O2)
2. hydrogen peroxide (H2O2) |
|
|
superoxide is more __________ than hydrogen peroxide
|
reactive
|
|
|
superoxide and hydrogen peroxide react with:
|
*everything* in your body
|
|
|
3 enzymes used to detox ROS:
|
1. superoxide dismutase
2. catalase 3. peroxidase |
|
|
what does superoxide dismutase do?
|
creates O2 and **hydrogen peroxide**
|
|
|
what does catalase do?
|
makes water and O2 *gas* out of H2O2
|
|
|
what does peroxidase do?
|
makes H2O2 into *water* - no gas
|
|
|
classification of bact. based on O2: 5 classes =
|
1. obligates anaerobes
2. aerotolerant anaerobes 3. facultative anaerobes 4. obligate aerobes 5. microaerophilic organisms |
|
|
the most medically-relevant of these are:
|
facultative anarobes
e.g. E. coli |
|
|
obligate anaerobes cannot:
|
grow in O2
(not protected from its toxicity) |
|
|
aerotolerant anaerobes:
(2) |
CAN grow in O2, but it's *inefficient*
=> grow much better in anaerobic environment |
|
|
facultative anaerobes:
|
grow *better* in O2 than without it
|
|
|
microphilic organisms *require O2 but:*
|
*can only tolerate it a little*
|
|
|
selective media only permit the growth of:
|
desired kinds of bact.
|
|
|
differential media grow all sorts of bact., but provide:
|
markers to distinguish them
|
|
|
Beta hemolysis =
|
complete hemolysis
- alpha = partial |
|
|
antimicrobial =
|
natural or synthetic cmpd that inhibits the growth of susceptible microorganisms
|
|
|
antibiotics are cmpds that are produced in:
|
**living organisms**
- fall under antimicrobials |
|
|
bacteriostatic bact. inhibit:
|
bact. growth, so that the immune system can kill them off.
|
|
|
at low-enough concentration, bacteriocidal antimicrobials can be:
|
b-static
|
|
|
the minimum inhibitory concentration =
|
the lowest concentration of drug needed to prevent the growth of a given strain
|
|
|
bact. persistence ~
|
some of the bact. not killed or inhibited => resistance => multiply again
|
|
|
3 mechanisms of antimicrobial resistance:
|
1. inactivate the drug enzymatically
2. alter what the drug is targeting 3. decrease exposure to drug |
|
|
inactivation of the drug is acquired:
|
from another source
|
|
|
altering the drug target is acquired:
(2) |
horizontally or through mutation
- as is decreasing exposure to the drug |
|
|
antimicrobials can target the cell wall of bact, specifically by targeting:
(2) |
the peptides that link the sugars,
or the enzymes that link them together |
|
|
what are Penicillin Binding Proteins?
(PBP's) |
bact. proteins that join peptides of cell walls together
|
|
|
what are B-lactams?
|
a class of natural and synth. antimicrobials that target bacterial cell wall-building enzymes
|
|
|
B-lactam ring mimics:
|
the D-Ala-D-Ala seq. of peptides that PBP's join together
|
|
|
when PBP's see B-lactams, they:
|
bind and *become inactivated*
|
|
|
5 classes of B-lactams, based on side chains:
|
1. penicillins
2. cephalosporins 3. carbapenems 4. monobactams 5. clavams |
|
|
clavams are very resistant to:
|
most B-lactamases
(except New Delhi) |
|
|
3 bact. strategies to resist B-lactam:
|
1. inactivate B-lactam (most common response)
2. penicillin-resistant PBP's 3. dec. permeability to B-lactams |
|
|
how do bact. inactivate B-lactams?
|
via **B-lactamases**
|
|
|
how do B-lactamases inactivate B-lactams?
|
they **cleave the lactam ring**
|
|
|
extended-spectrum B-lactamases =
|
mutated lactamases that have a broader range of B-lactam targets
|
|
|
***what is clavulanic acid?***
|
an ancillary drug used to *inhibit* B-lactamases
- they look like B-lactams, tricking the lactamases into binding them |
|
|
2 examples of bact. that have developed PBP's:
|
1. N. gonorrhea (mutated PBP's)
2. MRSA (acquired them horizontally) |
|
|
decreased permeability to a drug takes the form of spontaneous mutations in:
|
porin genes
|
|
|
ability to increase efflux of drugs occurs via:
|
horizontal acquisition of a new pump
|
|
|
which bact. has all 3 mechanisms of Resistance?
|
**N. gonorrhea**
|
|
|
some people are allergic to B-lactam; the rxn can be:
|
immediate (hours/rash)
or non-immediate (days/skin eruptions) use a skin test to check for allergy |
|
|
4 other types of cell-wall antimicrobials:
|
1. glycopeptides
2. bacitracin 3. cycloserine 4. phosphonomycin |
|
|
2 best examples of glycopeptides:
|
1. vancomycin
2. teichoplanin |
|
|
glycopeptides are primarily used against:
|
GP bact.
|
|
|
mechanism of vancomycin and teichoplanin =
|
inhibit cell wall synthesis by binding to D-Ala-D-Ala
|
|
|
vancomycin-resistant enterococci can change D-Ala-D-Ala to:
|
D-Ala-D-Lac,
but at a great expense |
|
|
**there are no known enzymes that inactivate:**
|
glycopeptide antibiotics
|
|
|
topical antimicrobials like bacitracin prevent:
|
peptidoglycan synthesis
- generally used against GP's |
|
|
what does cycloserine do?
|
inhibits synth. of D-Ala-D-ALa
|
|
|
what does phosphomycin do?
|
inhibits synth of sugars of the cell wall
|
|
|
what bact. do isonazaid and ethambutol target?
|
TB
- a type of mycobacterium |
|
|
some antimicrobials target the palsma membrane; best example =
|
daptomycin
- a lipopeptide |
|
|
what does daptomycin do?
|
attaches to plasma membrane, forming pores ==> bact. lysis
|
|
|
daptomycin is no good for:
|
pulmonary infections
|
|
|
why isn't daptomycin useful for pulmonary infections?
|
it's neutralized by sft
|
|
|
daptomycin is good for:
|
skin infections
|
|
|
daptomycin is used ONLY against:
|
GP's
(can't penetrate outermembrane of GN's) |
|
|
microbiota = microflora =
|
ALL the microorganisms of a particular site or period of time
|
|
|
microbiome =
|
collective genome of given microbiota
|
|
|
normal flora = commensal flora =
|
good microorganisms that are normally associated with healthy persons
|
|
|
"germ free" includes being free from:
|
normal flora
|
|
|
microbiota of the human body are an:
|
organ
|
|
|
intestines hold the most normal flora, followed by:
|
the mouth
|
|
|
at a ratio of 1000:1, most of the normal flora are by far:
|
anaerobes
|
|
|
what is 16S?
|
a ribosomal RNA
- an essential component of bact. ribosomes |
|
|
ALL bact. have:
|
16S
- used for identification |
|
|
there are greater than ______ different bact species in the intestines
|
1000
|
|
|
the human gut also includes _____ viral species
|
1200
|
|
|
humans are germ-free at birth; almost immediately,
|
we start acquiring normal flora
|
|
|
past 1 year from birth, a child's microbiota resemble:
|
an adult's microbiota
|
|
|
6 positive effects of normal flora:
|
1. they stimulate production of AB's
2. production of Vit. K 3. increase nutrient absorption 4. stimulate development of intestinal villi 5. improve the immune system 6. protect against invading bact. |
|
|
if colonized by N. lactamica, you're less likely to be infected by:
|
N. gonorrhea
|
|
|
free of normal flora =>
|
immune disease later in life
|
|
|
mal effects of normal flora:
(2) |
1. cause infection if they get into a place they shouldn't be
2. may cause autoimune disease if they share antigens with tissue |
|
|
what's one autoimmune condition caused by normal flora?
|
Irritable Bowel Syndrome
|
|
|
what kind of bact. is the leading infectious cause of mortality in newborns?
|
Group B Strep
- even though they're commensal in adults |
|
|
Group B Strep are found in:
(2) |
1. gut
2. female genital tract |
|
|
antibiotic treatments increase risk of other infection because:
|
they kill the normal flora, thereby freeing up the space they occupied for pathogenic bact.
|
|
|
probiotics =
|
living organisms that prevent or treat infection
|
|
|
example of probiotic =
|
lactobasillus in yogurt
- treats colitis and urinary tract infections |
|
|
prebiotics =
|
dietary ingredients that stimulate growth/metabolism of health-promoting GI bact.
|
|
|
good example of a prebiotic =
|
human milk
|
|
|
sessile bact =
|
bact growing in a biofilm
|
|
|
planktonic bact =
|
free-floating bact
|
|
|
biofilm =
|
population of bact. adhering to surfaces
|
|
|
biofilms in depth:
(4) |
1. bact. are encased in a polysaccharide coating
2. enough moisture, and they'll grow 3. **highly resistant to antibiotics** 4. vast majority of bact. in nature live in them |
|
|
bact. living in biofilms are difficult to eradicate, even if:
|
antibiotics will kill that same bact. in planktonic state easily
|
|
|
MIC for biofilm bact may be ______-fold higher than for the planktonic version
|
1000-fold
|
|
|
5 stages of biofilm formation:
|
1. reversible attachment
2. irreversible attachment 3. polysaccharide production 4. growth of 3D structure 5. dispersal |
|
|
"foreign body infection" =
|
biofilm growing on implant or catheter
|
|
|
the immune response against foreign body infections only damages:
|
the surrounding tissues
- doesn't kill biofilm - needs to be removed surgically to clear infection |
|
|
why are biofilms so resistant?
(3) |
1. antibiotics have poor penetration against them
2. physiological HETEROgeneity of one bact. to the next 3. some bact have R genes that are expressed ONLY in when living in biofilm |
|
|
otitis media = ear infection =
|
biofilm problem
|
|
|
3 types of otitis media:
|
1. acute
2. recurrent chronic 3. chronic OM with effusion |
|
|
acute OM responds well to:
|
antibiotics
|
|
|
chronic OM: symptoms keep coming back because:
|
antibiotics are only killing the bursts of planktonic bact. from the biofilm
- once antibiotics are discontinued, a new burst can be sent out => symptoms return |
|
|
chronic OM with effusion: air in the middle ear is:
|
replaced with fluid
- persists from weeks to months - children are asymptomatic except for hearing loss - need to put tube in to drain fluid and allow immune system to work |
|
|
2 strategies against biofilms:
|
1. coat implants with silver or antibiotics
2. use combos of antibiotics against them |
|
|
no test is 100% perfect; they all =>
|
false positives, false negatives
|
|
|
positive test results are more accurate when:
|
the *pre-test probability* is *higher*
|
|
|
what are false positives bad?
(4) |
1. inappropriate antibiotics are given
2. leads to more expensive testing 3. increases the length of stay 4. may cause you to miss *correct* diagnoses |
|
|
how do blood cultures impact pre-test probability?
(4) |
1. giving antibiotics prior to blood draw (false n)
2. too small a volume of blood (false n) 3. improper cleaning of venipuncture site (false P) 4. serology when ticks are dormant (false p) |
|
|
testing process has 3 steps:
|
1. pre-analytic
2. analytic 3. post-analytic |
|
|
errors are most frequent at:
|
the pre-and post-analytic stages
|
|
|
4 key reasons for medical errors due to lab testing:
|
1. ordering the wrong test
2. ordering no test at all 3. misinterpreting results 4. not looking at or acting upon results quickly |
|
|
critical lab value =
|
one that demands immediate attention
|
|
|
acid fast staining =
|
primary stain for MYCObact.
|
|
|
a positive acid fast stain does NOT mean:
|
that you have TB
|
|
|
calcaflour ~
|
fungal cell walls
|
|
|
serology detects:
|
AB's
|
|
|
NAATA is a test used for:
(3) |
1. TB
2. enterovirus 3. influenza |
|
|
NAATA will determine if TB is:
|
multi-drug resistant
|
|
|
bacterial reservoir =
|
environmental *source* of infectious agent
- eggs, pond, family, etc. |
|
|
colonization =
|
bact. growing on/in host without adverse effects
|
|
|
infection =
|
association b/w bact and host that results in adverse effects
|
|
|
virulence =
|
pathogenic potential of an organism
|
|
|
pathogenesis =
|
**process** by which an organism causes disease
|
|
|
virulence factors/determinants =
|
bact. products or processes that contribute to the ability to cause disease
- distinct from housekeeping functions** |
|
|
5 steps of pathogenesis:
|
1. transmission
2. adherence/colonization 3. local proliferation 4. tissue damage 5. dissemination |
|
|
transmission of bact. is called exogenous if the bact comes from:
|
the environment
|
|
|
endogenous transmission refers to:
|
normal flora getting into where they shouldn't be
|
|
|
facultative intracellular pathogens can grow:
|
extra- OR intracellularly
|
|
|
tissue damage from pathogens occurs via:
(4) |
necrosis, apoptosis, imm. resp., exotoxins
|
|
|
dissemination =
|
spread to other tissues
|
|
|
septicemia =
|
presence/persistence of pathogenic organisms or their toxins in the blood
|
|
|
infectious bact. must overcome:
(5) |
physical barriers, normal flora, chemical factors, II, and AI
|
|
|
bact. require:
|
iron
|
|
|
**3 examples of virulence factors/determinants:**
|
1. type IV pili
2. toxins 3. avoiding host's immune system |
|
|
type IV pili are:
|
adhesins
|
|
|
adhesins =
|
surface organelles
|
|
|
3 functions of Type IV pili:
|
1. formation of biofilms by helping bact. aggregate
2. adherence 3. motility |
|
|
motility of bact allows them to:
|
spread across a surface/tissue
|
|
|
2 examples of toxins:
|
1. Diphtheria / A-B toxin
2. Type-3 Secretion System |
|
|
Diphtheria toxin is expressed by:
|
Coryne diphtheria, causing the disease of the same name
|
|
|
what immunizes you against diphtheria?
|
DTaP
|
|
|
C. diphtheria infect:
|
the throat, causing formation of pseudomembranes
- release an extremely potent toxin |
|
|
pseudomembranes = collection of:
(3) |
bact, immune cells, and fibrin
|
|
|
Diphtheria/AB toxin = 2 subunits joined by:
|
disulfide bond
|
|
|
B fragment of AB toxin =
|
adhesin
- binds to susceptible host cell |
|
|
A fragment of AB toxin =
|
***enzyme that inhibits host cell synthesis***
(released from B into the cytoplasm) |
|
|
T3SS =
|
multiprotein "toxin syringe"
|
|
|
what T3SS do?
|
injects exotoxins into the host cell
|
|
|
best example of T3SS bact. =
|
Pseudomonas aeruginosa
|
|
|
Pseudomonas aeruginosa causes:
|
pneumonia (via T3SS), by paralyzing/killing phag. cells
- w/o T3SS, it's not pathogenic |
|
|
how does Listeria monocytogenesis avoid the host immune system?
|
tricks the imm. system to tphag. it
- inside the immune cell, uses phospholipases to rupture the phagosome - use actin polymerization to propel themselves into the next cell (use phospholipases to break that cell membrane) |
|
|
L. monocytogenes takes over the host's:
|
actin polym. machinery via ActA on its surface
|
|
|
what's the best example of a bact. that has all 3 virulence factors?
|
EPEC
(enterotoxic E. coli) |
|
|
EPEC MO:
(6) |
1. pili cause initial adherence
2. T3SS injects Tirs 3. Tirs become receptors for intimins 4. with tight adherence, surrounding microvilli dissolve 5. actin polymerizes in the cytoplasm 6. pedestal forms |
|
|
what is the energy source for protein translation?
|
GTP
|
|
|
7 different bact. translation inhibitors:
|
1. aminoglycosides
2. tetracyclins 3. macrolides 4. lincosamides 5. streptogramins 6. oxazolidinones 7. fusidic acid |
|
|
how do aminoglycosides work?
|
they bind to 16S rRNA mlcl in the 30S subunit, causing mis-translation
=> non-functioning bac.t prot. |
|
|
aminoglycosides are bacterio-
|
cidal
|
|
|
R to aminoglycosides is usually:
|
drug modificaiton
|
|
|
another R mechanisms against aminoglycosides =
|
mutation of 16S
|
|
|
**tetracyclines:**
(4) |
1. lipophilic => easily pass through bact. membrane
2. also bind to 16S 3. bacteriostatic 4. occlude the A site |
|
|
**tetracyclines are _________________ antibiotics;
|
***broad-spectrum***
- fight both GP AND GN bact. |
|
|
**main R mechanism to tetracyclines =
|
efflux
|
|
|
another notable R to tetracyclines =
|
making ribosomal protection proteins (RPP's), which dislodge tetracyclins
|
|
|
drug inactivation is NOT a common R mech. against
|
tetracyclins
|
|
|
what do macrolides do?
(2) |
1. bind to 23S mlcl of 50S ribosomal subunit
2. => make nascent peptide and ribosome dissociate |
|
|
macrolides are generally:
|
bacteriostatic,
though they can be cidal for some bact. |
|
|
2 popular kinds of macrolides:
|
1. erythromycin
- natural antibiotic 2. azithromycin (z-pak) - semi-synthetic |
|
|
notable R to macrolides =
|
expressing MLSb
via mutations to various prot's, which alters the target |
|
|
MLSb confers:
|
multi-drug resistance
|
|
|
MLSb confers resistance against the following kinds of drugs:
(3) |
1. macrolides
2. lincosamides 3. streptogramins |
|
|
best example of lincosamide =
|
clindamycin
|
|
|
lincosamides have the same mode of action as:
|
macrolides
|
|
|
streptogramins have 2 components, A and B:
|
A inhibits transpeptidation
B blocks exiting peptide |
|
|
streptogramins are bacterio-
|
cidal
|
|
|
apart from MLS, streptogramins are resisted by:
(2) |
1. inactivating the B component
2. efflux pumps for A component in GP bact. |
|
|
what do oxazolidinones do?
|
inhibit a functioning ribosome by blocking small and large subunits from joining
|
|
|
best example of oxazolidinones =
|
linezolid
|
|
|
R to oxazolidinones is ONLY via:
|
target alteration
- NO inactivation or exposure mechanisms |
|
|
fusidic acid is synthesized by:
|
fungi
|
|
|
there are NO known inactivation mechanisms against:
|
fucidic acid
|
|
|
what do quinolones and fluoroquinolones do?
|
inhibit bact. transcription by
inhibiting bact. topoisomerases |
|
|
what do rifamycins do?
|
inhibit bact transcription by
blocking elongation of transcripts by binding to RNAP => aborted transcription |
|
|
R to rifamycins occurs ONLY via:
|
mutations in bact. RNAP
|
|
|
another way to defeat bact. is by inhibiting:
|
synthesis of critical bac.t metabolites,
like folate |
|
|
folate (B9) is required for:
|
synthesis of DNA
|
|
|
since humans don't make folate, we can target:
|
folate and the enzymes that make it
|
|
|
what is PABA?
|
a folate precursor
|
|
|
what are sulfa drugs?
|
**drugs that compete with PABA for the folate pathway**
|
|
|
which two drugs are often given together to completely stop folate synthesis?
|
sulfanilamide and trimethoprim
- NO known drug inactivation of them |
|
|
main R to sulfa drugs =
|
increase in PABA production
|
|
|
prodrugs =
|
drugs that are administered in an inactivated state
- activate in vivo |
|
|
prodrugs release:
|
toxic, reactive nitrogen species
|
|
|
3 examples of prodrugs:
|
1. Nitrofuran
2. metronidazole 3. methenamine |
|
|
combo antibiotic therapies:
(2) |
1. prevent R
2. used in emergency situations in which bact are unknown |
|
|
3 good synergistic interactions of antibiotics:
|
1. cell wall-targeting + intracellular targeting
(e.g. B-lactam + aminoglycoside) 2. agents that act at diff. points of the same pathway 3. agenst that inhibit R mechanisms (e.g. B-lactam + calvulanic acid) |
|
|
**in Staph aureus, erythromycin + linco or strepto given together can confer:**
|
MLSb
- **but ketolides and lincosamides do NOT** |
|
|
MRSA =
|
methycillin-resistant Staph aureus
= most dominant form of hospital-acquired infection |
|
|
VRSA =
|
vancomycin-resistant Staph aureus
|
|
|
just b/c a resistance mechanism is possible, doesn't mean:
|
an organism will thrive with it
|
|
|
what are viruses composed of?
(4) |
1. prot.
2. nucleic acids 3. sugars 4. lipids (if enveloped) |
|
|
what 2 critical functions does the viral genome encode?
|
1. genome replication/assembly
2. modulation of host defenses |
|
|
what 3 important functions does the viral genome NOT encode?
|
1. protein synthesis
2. membrane synthesis 3. energy metabolism |
|
|
lipid-enveloped viruses are pleomorphic; their shape changes depending on:
|
which cell type they are made in
|
|
|
virion =
|
complete form of a virus
|
|
|
basic viral structural unit = capsid =
|
protein coat
|
|
|
all virions contain at least ONE:
|
protein coat,
capsid or nucleocapsid (HIV has both) |
|
|
2 types of coats:
|
1. icosahedral/spherical/closed
2. helical/rod-shaped/open at one end |
|
|
helical/open viruses have, in theory, no limit to:
|
nucleic acid packaging
(open at one end) |
|
|
***of the spherically-shaped viruses, the only circular shape observed is:
|
icosahedral
(20-faced) |
|
|
envelopes of enveloped viruses are derived from:
|
**host membranes**
- either plasma membrane or organelle membrane => your membrane presented to your immune systems (sneaky) |
|
|
hi
|
Casey.
|
|
|
envelopes contain:
(2) |
1. glycoprot's
2. host cell prot's |
|
|
host cell prot's on envelope surface =>
|
confusing the immune system
|
|
|
glycoproteins are used for:
|
attachment
|
|
|
viral attachment:
|
1. viruses move by Brownian motion
2. the more viral receptors they possess, the more susceptible cells are to infection 3. goal of attachment is to get from 3D to 2D |
|
|
enveloped viruses enter the host cell in 2 ways:
|
1. membrane fusion that dumps virus in
(used by parainfluenza) 2. receptor-mediated endocytosis (used by influenza) |
|
|
in receptor-mediated endocytosis, clathrin-coated pits become:
|
endosomes => late endosomes => lysosomes
|
|
|
***as an endosome gets more acidic, the change in pH =>
|
viral envelope fusing with the endosome => virus gets released to cytoplasm
|
|
|
non-enveloped viruses get into host cells via:
|
receptor-mediated endocytosis
|
|
|
best example of non-enveloped virus =
|
adenovirus
|
|
|
adenovirus' penton base disrupts:
|
the endosome, releasing it into the cytoplasm
|
|
|
once a virus gets into the cytoplasm, it hijacks:
|
the cell's transport system to get the nucleic acid where it needs to go
|
|
|
cytopathic effect (CPE) =
|
degenerate appearance or cell death due to viral replication and inhibition of host cell's macromlcl synthesis
|
|
|
the concentration of infection virus particles is measured in:
|
plaque-forming units (pfu's)
|
|
|
the ability to detect a virion falls rapidly once:
|
you're infected and it's entered the cytoplasm (it breaks apart into components)
|
|
|
during the eclipsed period, the viruses are:
|
undetectable
|
|
|
extracellular viruses are not seen for:
|
longer than intracellular ones
|
|
|
viral replication cycle:
(7) |
1. adsorption
2. entry 3. uncoating 4. gene expression 5. gene replication 6. maturation (envelopes only) 7. egress/release |
|
|
to adsorb means:
|
to gather on the surface of
|
|
|
**negative sense RNA virsus don't completely:**
|
uncoat
|
|
|
as a result of uncoating, all physical traces of the virion are:
|
lost
|
|
|
***ALL viruses need their nucleic acid to become:***
|
mRNA
|
|
|
how do DNA viruses make their DNA into mRNA?
|
they take over host's RNAPII
- also take over transcription and translation prot's => send new mRNA to the cytoplasm |
|
|
**exception of DNA virus mechanism:**
|
pox viruses have their OWN DdRP
- replicate in the cytoplasm |
|
|
how do positive sense RNA viruses make mRNA?
|
**their nucleic acid IS the mRNA**
|
|
|
how do negative-sense RNA viruses get their RNA to become mRNA?
|
***they encode their own RdRP***
=> makes a positive-sense RNA |
|
|
negative-sense viruses don't uncoat completely because:
|
otherwise thir RdRP would escape into the cytoplasm
|
|
|
***exception to negative-sense mechanism***
|
hepatitis delta virus' RNA is transcribed by the **host RNAPII** in the nucleus
|
|
|
retroviruses also carry:
|
positive-sense RNA
|
|
|
retroviruses use RT to:
|
convert their RNA into DNA, which is then transcribed to RNA
|
|
|
RT is composed of 3 things:
|
1. RdDP
2. RNAse 3. DdDP |
|
|
***which retrovirus enzyme inserts proviral DNA into the host genome?***
|
**integrase**
|
|
|
retrovirus' mRNA is modified post-transcriptionally by:
|
viral proteins
|
|
|
viral genome replication is achieved via:
|
host cell enzymes OR viral-encoded enzymes
|
|
|
ALL DNA viruses encode:
|
at least one replication protein
- some encode their own DNA Polymerase |
|
|
ALL positive-sense RNA viruses:
(2) |
1. replicate in the cytoplasm
2. encode RdRP |
|
|
positive-sense RNA viruses make:
|
intermediate neg-sense RNA first, then use it as a template to make MANY copies of pos-sense RNA, to be packaged into virions or be translated
|
|
|
all neg-sense RNA viruses encode:
|
RdRP (except, of course, for hep delta)
|
|
|
neg-sense RNA viruses make:
|
pos-sense RNA, which then serves as mRNA OR is converted back into neg-sense
|
|
|
RdRP's don't have:
|
proof-reading capabilities
=> error-prone => RNA viruses are quasi-species |
|
|
retroviruses' proviral DNA is made via RT at:
|
the *beginning* of the replication cycle
=> viral mRNA stemming from this proviral DNA is packaged into newly-formed virions along with other RT's |
|
|
hepadnaviruses use RT at the:
|
END of the rep. cycle
- e.g. hepatitis B |
|
|
hepatitis B (hepadnavirus) MO:
|
original viral DNA => mRNA via host RNAPII => packaged with RT's => proviral DNA is made
|
|
|
progeny nucleocapsid formation ~~
|
accumulation of capsid structural proteins where nucleic acids are being converted to mRNA
|
|
|
capsid formation is achieved via:
(2) |
self-assembly or host prot. scaffold
|
|
|
maturation of a virus refers to:
|
enveloped viruses receiving their envelopes
|
|
|
some viruses mature:
|
intracellularly;
others, on the cell surface |
|
|
egress/release of viruses: the direction of release (apical vs. basolateral) has implications for:
|
pathogenesis (i.e. localized vs. disseminated infection)
|
|
|
viral enzymes are often necessary to complete:
|
the release process
|
