Microbiology: Bacteria And Intro To Infection

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Why do all bacterial populations contain some variety

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1. Mutation of existing genetic information
2. Transfer of additional genetic material into a cell by some other than chromosomal replication during cell division (basically Horizontal Transfer)

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Infection

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The establishment of a pathogenic bacterium, virus, or fungus in its host after invasion

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pathogenicity

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the ability to cause disease

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virulence

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extent of pathogenicity (how bad the disease is)

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flora

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organisms that routinely colonize appropriate surfaces without causing disease

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prions

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*misfolded protein that causes normal proteins to fold abnormally which affects the other protein's ability to function
* resistant to inactivation; leading to iatrogenic (describes a symptom or illness brought on unintentionally by something that a doctor does or says) spread
*spread by eating contaminated meat (nervous tissue)

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progress of infectious diseases

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* the association of microorganisms with infectious disease
* the implementation of public health/sanitation measures
* improvements in health education

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Why is it still important?

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* Increase of pathogen resistant to multiple antibiotics
* In less developed countries, infectious diseases are still the primary cause of death
* Emergence of previously unknown diseases
* Immune suppressed patients
* Biohazard response vs. handling your mail

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Why new emerging disease?

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* Adaptation and change by pathogens; hastened by increased antibiotic useà increase in resistant mutants (selective pressure)
* Technological developments which increase the likelihood of disease emergence (Food Industry)
* Increasing human numbers; increasing urbanization
*  role of international travel and commerce in the rapid spread of pathogens (ex. SARS)
*  human spread into new environments, bringing us into contact with previously unknown pathogens and vectors (ex. *Environmental change/ global warming)

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what are cell surface functions?

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a. Sensing (react to the outside info to change their behaviour)
b. Regulate transport of materials in/out cell
c. Protection (from outside environment. Ex. Osmotic pressure, UV light, from drying out)
d. Control cell’s location (via movement and attachment (pilli))

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Why do all bacterial populations contain some variety?

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*Mutation of existing genetic information
* Horizontal transfer of additional genetic material into a cell by some mechanism other than chromosomal replication during cell division (transformation, transduction, conjugation)

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hypermutators

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pathogens which have defective DNA repair genes and so a tendency to rapidly develop mutations leading to resistance to multiple antimicrobials

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spontaneous mutations

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natural errors in DNA replication
-occur in range of 1:10^6 to 1:10^9

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induced mutations

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speed up the mutation rate

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recombinants

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Cells which integrate such received DNA into their DNA

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Basic steps in integration of exogenous DNA into the chromosome:

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* recipient DNA is cleaved by DNAse
* matching donor fragment is linked to recipient strand via DNA ligase
* DNAse then degrades replaced recipient sequences

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Antimicrobial resistance genes are those which code for:

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* Enzymatic breakdown of antimicrobial agent
* Alteration of target molecule on the pathogen, disrupting the agent’s ability to bind
* Reduced uptake or enhanced removal of the agent from the pathogen

 

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Transposons

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small segments of DNA that can move from one
region to another region of the same chromosome or to a different
chromosome or a plasmid.
17. Transposons are found in chromosomes, in plasmids, and in the
genetic material of viruses. They vary from simple (insertion
sequences) to complex.
18. Complex transposons can carry any type of gene, including
antibiotic-resistance genes, and are thus a natural mechanism for moving genes from one chromosome to another.

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How are bacteria counted?

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* viable count (often based on diluted sample)
* microscopic cell count (growth of a population of bacteria is a closed system)
* count based on cell mass

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The phases of exponential growth:

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* Lag phase - metabolic ‘gearing up’ by bacteria; turning on/off genes
 
* Log phase - the rate of division and the duration of the log phase are restricted by conditions and resources (we need to make log phase as short as possible; need to back them go into stationary and death phase as soon as possible; use of antimicrobial)
 
* Stationary phase - nutrients are dwindling, toxic waste products are building up
 
* Death phase - Size of the viable population begins to fall (the bacteria has run out of food.)

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Calculating numbers of bacteria

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* THE formula: Nt = No x 2n
No = number at time 0
Nt = number at time t
n = number of generations (elapsed time/ generation time)

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Bacterial Metabolism - Bacteria obtain energy and carbon in various ways:

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Energy
* Phototroph - uses light
* Chemotroph - uses oxidation reduction reactions
 
Carbon source
* Autotroph - uses CO2
* Heterotroph - uses organic compounds

 

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Anabolism

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(synthesis)
* Range of abilities to synthesize among the pathogens
* simple to fastidious growth requirements, e.g., requiring growth factors
* building blocks to macromolecules
* General requirements of C, O, H, N, S, P
* Varying additional requirements: K, Mg, Fe, co-enzyme components (trace elements, growth factors)
* Metabolic pathway of choice is controlled via enzyme regulation (not passive)

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Catabolism

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(degradation)
* Multiple sources may serve as C, N and energy sources
* Compounds may be degraded and assimilated by multiple pathways with multiple control mechanisms in play
Mechanisms for generating metabolic energy: fermentation, respiration,

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Fermentation

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* Definition: Catabolic reaction in which the primary electron donor and ultimate electron acceptor are organic and ATP is produced by substrate level phosphorylation
* ATP generation is coupled to chemical rearrangement of organic compounds; resulting fermentation products have the same elemental composition as the substrates (ex. 1 glucose (C6H12O6) > 2 lactic acid (C3H6O3)
* Many compounds are suitable; many pathways
* Low energy yield; lots of waste products

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Respiration

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* Definition: Catabolic reaction in which the electron donor may be organic or inorganic and the final electron recipient is inorganic, often oxygen (aerobic respiration) but may be CO2, sulfate or nitrate (can occur anaerobically; less efficient than aerobically, unusual among human pathogens)
* Electrons are passed from a chemical reductant (typically NADH) to a chemical oxidant (typically oxygen) through a set of electron carriers within the bacterial cell membrane (mitochondria of eukaryotes) a.k.a. electron transport phosphorylation
* Microorganisms which are unable to use ETP must hydrolyze ATP; thus aerobic respiration is much more efficient at energy production from substrate utilization

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Obligate Aerobes

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-only aerobic growth; oxygen required
-growth occurs only where high concentrations of oxygen have diffused into the medium
- presence of enzymes catalase and superoxide dismutatase (SOD) allows toxic forms of oxygen to be neutralized; can use oxygen
-cannot carry out fermentation or anaerobic respiration

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Facultative Anaerobes

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-both aerobic and anaerobic growth; greater growth in presence of oxygen
-growth is best where most oxygen is present, but occurs throughout tube
-presence of enzymes catalase and SOD allows toxic forms of oxygen to be neutralized; can use oxygen

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Obligate Anaerobes

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-only anaerobic growth; ceases in presence of oxygen
-growth occurs only where there is no oxygen
-lacks enzymes to neutralize harmful forms of oxygen; cannot tolerate oxygen

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Aerotolerant Anaerobes

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-only anaerobic growth; but continues in presence of oxygen
-growth occurs evenly; oxygen has no effect
- presence of one enzyme, SOD, allows harmful forms of oxygen to be partially neutralized; tolerates oxygen

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Microaerophiles

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-only aerobic growth; oxygen required in low concentration
-growth occurs only where a low concentration of oxygen has diffused into medium
-produce lethal amounts of toxic forms of oxygen if exposed to normal atmospheric oxygen.

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The role of bacterial endospores

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* Spores are only found in a few species of human pathogens
* Spores are able to survive heat, drying, UV irradiation, disinfectants
* Spore formation involves shutdown of vegetative genes, and the engagement of sporulation genes
* Process takes several hours; usually brought on by lack of C or N
* Receptors sense return of favorable conditions

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Virulence mechanisms of microorganisms

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* resistance to antibiotics
* production of substances harmful to the host
* evasion of the immune response
* induction of harmful immune response
* adherence to or invasion of host cells

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bacterial exotoxins

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* secreted into the environment
* protein based; highly antigenic
* several modes of action
* Damage cell directly
* Disrupt cell communication
* Interfere with internal cell processes
* produced by gram positives and gram negatives
* very specific
* often plasmid or phage encoded
* common mechanism: A + B subunit toxin

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Endotoxins

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* LPS in outer membrane of gram negatives (outer/ cell wall, periplasm, inner membrane)
* released only when cells are damaged or killed
* low antigenicity
* low specificity
* LPS three part composition: core polysaccharide (highly conserved) + specific polysaccharide (responsible for serologic diversity) + Lipid A
* LPS triggers a multitude of host immune responses
* induces cytokines, e.g., TNF and IL-1
* activates complement
* triggers clotting mechanism
* induces fever; drops blood pressure
* Amount of LPS is important - low level exposure stimulates immune system; high level exposure - endotoxic shock develops and DIC (disseminated intravascular coagulation)

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Siderophores

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* iron-binding compounds excreted by pathogens under iron stress
* host actively sequesters iron during infection to limit growth of pathogens
* Siderophores are iron binding compounds secreted by pathogens under iron stress.
* Host actively sequesters iron during infection to limit growth of pathogens

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Host immune response - avoidance or deactivation by pathogens

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nhibition of:
* Host cell signal transduction
* Host WBC chemotaxis
* Opsonizatoin by host antibodies
* Phagocytosis by host WBC
* Phagocytic destruction within WBC 
* induction/suppression of host cell apoptosis
* intracellular replication
* antigenic manipulation (abuse cells ability to recognize self)
*  antigenic mimicry
*  antigenic masking (teichoic acid is very antigenic; covered by capsule or lesser immunogenic molecule to hid)
*  anigenic alteration

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Host immune response to pathogen - responsible for the disease process (pathology from immune activation by the pathogen)

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* endotoxic shock (in some cases this works to the organisms advantage or not)
* cross-reacting antibodies
* immune complexes
* Inflammation (recruiting cells to the area; increased WBC; redness; fever)
* Superantigen (no specific reaction. Nature of the immune response is overwhelming)

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Virulence factor summary

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* Again pathogenic traits in bacteria are due to the action of genes coding for specific structures and substances
* Traits can be selected form within a population thus the population in general acquires that trait
* Factors may be able to be turned on and off by individual cells as the sense extracellular conditions
* Some organisms routinely turn factors on and off in anticipation (phase variation)
* Virulence factor can spread rapidly via plasmids and transposons especially under selective pressure
* May also become more widespread among multiple populations
* Clusters of virulence genes are known as "pathogenicity islands"- with a single promotor, pressure on one gene results in retention of entire cluster.

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What determines whether an encounter with a pathogen causes clinical disease?

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·  Age/immune status of host [little kids and the elderly]
· Genetic makeup of the host
· Route/ site of exposure
· Microbial load (size of exposure)
· Genetic makeup of the microorganism

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Pathogen

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an organism able to cause disease in a host
· Some organisms are strict or frank pathogens;
· Others are opportunistic pathogens
§ Same host in debilitated condition
§ Different tissue within the host
Opportunistic pathogen- right pathogen at the wrong place (ex. E. coli) 

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Virulence

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Either invading your cells or creating toxin that harm your cells
· Pathogenic traits in bacteria are due to the action of genes coding for specific structures and substances (virulence factors)
· In general, virulence in bacteria is associated with invasiveness and/or toxigenicity
· In general, virulence in viruses is associated with the degree and nature of host cell involvement
Also: host immune response as a virulence factor

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Iceberg concept of infection

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Most infections are subclinical

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various courses of infection

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•acute
•chronic/persistent infection with shedding (Typhoid fever)
•latent (herpes, tuberculosis, and shingles)
•persistent slow infection (following acute)-(HIV): microbe growth continues sometimes in privileged site
•persistent slow 'infection' (no acute)- (mad cow): continued slow microbial growth

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Endemic

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characteristic of a disease that exists continually at some level in an are

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Outbreak

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a sudden increase in the number of cases of a disease in a small, defined area

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Epidemic

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a sudden increase in the number of cases of a disease, typically in a larger area

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Pandemic

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a disease outbreak affecting a high percentage of people over most of the globe. Ex HIV

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Endogenous source

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from within the body

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Exogenous source

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from within the body

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Exogenous source

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from outside the body

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Nosocomial infection

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an infection acquired while visiting a hospital/health care facility

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Iatrogenic infection

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an infection introduced by a medical treatment

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Opportunistic pathogen

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a normally non-pathogenic microorganism which causes disease typically in an immunocompromised patient

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○ Why would an microorganism cause symptomatic diseases?

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○ Damage host cells release substances used by pathogen in reproduction
○ Directly assists in spread of pathogen progeny
○ coincidence