11.2 Bacterial Pathogenicity, Growth and Antibiotics Flashcards
Which surfaces of a host do commensal bacteria colonise?
All of them
What are two benefits to the host of commensal bacteria?
- Protection against pathogen
- Metabolic benefits (e.g. folate production by bifidobacterium)
How do commensal bacteria usually protect against pathogens?
Via competition for colonisation sites
What are some instances where opportunistic pathogens may infect a host?
- Trauma/tissue damage
- Infection/immunological insult
What is a pathogen?
An organism whose growth inflicts damage upon its host as a by-product of its nutrient gathering strategy
Describe indirect pathogenic damage
- Disturbs metabolic balance/nutrient acquisition
Describe direct pathogenic damage
- Bacteria secretes toxins
Pathogenesis
Mechanism of disease
Virulence
Capacity to cause disease/severity of symptoms
Two categories of structural and functional features of pathogens
- Promote competition
- Damage host and cause symptoms
What are the four phases of the pathogenic cycle?
- Transmission
- Colonisation
- Proliferation
- Evasion
List some disease transmission routes
- Direct contact
- Indirect contact
- Aerosol/respiratory
- Zoonotic
- Food-borne
- Faecal-oral
What is the infectious dose 50 of a bacteria?
The number of organisms required to infect 50% of individuals
What is inoculum size?
Amount of a pathogen an individual is actually exposed to
Give an example of an extracellular enzyme secreted by bacteria which have a role in pathogenesis
Beta haemolysin
What are the two types of bacterial toxins?
- Exotoxins (made and secreted during growth)
- Endotoxins (structural components that have toxic activity)
Which type of bacterial toxins are more toxic at low doses?
Exotoxins (e.g. neurotoxin, enterotoxin, hepatotoxin etc.)
What are the two broad groups of exotoxins
- Cytolysins (cause lysis of cells)
- Two component toxins (A-B) remember Christopher Wong -> disrupt cellular processes
When are endotoxins released? What influence does this have on medication?
- Released upon death of bacteria
- This means that too much antibiotics can be detrimental, since it leads to a whole bunch of dead bacteria
What are the three outcomes of infection?
- Clearance
- Asymptomatic carriage
- Symptomatic disease (potential long term impacts/death)
What factors affect the outcome of an infection?
- Immune status
- Prior exposure
- Diet
- Microbiome
What structures can antibiotic resistant genes be found in?
- Bacterial chromosomes
- Plasmids
- Mobile genetic elements (integrons and transposons; move into chromosomes or plasmids)
Describe transformation as a mechanism of antibiotic resistance propagation
- Transfer of plasmid DNA or a fragment of free DNA from a lysed cell to a living cell
What is genetic transduction? how common is this in spreading antibiotic resistance?>
- Transfer of genes between bacteria via bacteriophages
- Rarely involved in antibiotic resistance transfer
Other than antibiotic resistance, what other genetic information might be carried on an R plasmid?
- Sugar metabolism
- Heavy metal resistance
- Resistance to osmotic stress
How does the spread of resistance genes usually occur?
Acquisition of resistance genes from mobile genetic elements such as plasmids and transposons
Describe the mechanism of complex transposons
- Can contain antibiotic resistance genes
- Move rapidly between chromosome and plasmids in cell
- Move through a bacterial population (incl. across species)
Describe the mechanism of gene cassettes
- Can exist as separate genetic elements
- Can be integrated into transposons, integrons, or bacterial chromosome
Describe an integron
- Sequence of DNA which can contain resistance to antibiotics (as well as other things). .
- Integrase enzyme selectively adds genes to integron, thus adding genetic information to a bacterial cell
Describe the four phases of bacterial growth in an isolated system
- Lag (Cells adapt to new conditions, enzymes accumulate)
- Exponential phase (maximum constant growth rate)
- Stationary phase: Population reaches 10^7-10^9, and oxygen/nutrient demands can no longer be met. Slow death balanced by slow proliferation
- Death phase: number of viable cells drop as waste accumulates, death > proliferation
List factors that affect bacterial growth
- pH
- Temperature
- Osmolarity
- Nutrient availability
- Oxygen concentration
What are the five kinds of bacteria in terms of oxygen requirements?
- Strict anaerobe
- Facultative anaerobe
- Aerotolerant anaerobe
- Microaerophile
- Obligate aerobe
Which enzyme protects aerotolernat bacteria from oxygen free-radicals?
Superoxide dismutase
Which are the four mechanisms of inhibition by which antiobiotics achieve their effect:
Inhibit:
- Cell wall synthesis
- Protein synthesis
- Nucleic acid synthesis
- Certain metabolic pathways
Bacteriostatic vs Bacteriocidal antibiotics
Bacteriostatic: Inhibits growth
Bacteriocidal: Kills the bacteria
Give an example of a class of antibiotic that inhibit nucleic acid synthesis
Fluoroquinolones
Give an example of a class of antibiotics that inhibit cell wall synthesis
- Penicillins
Describe the mechanism of action of penicillins
- Bind to proteins involved in peptidoglycan assembly (so-called penicillin binding proteins: PBPs)
- Inhibits last step of cell wall synthesis
- Prevents cross-linking of peptidoglycan strands -> leads to lysis of cell
- Only acts on growing bacteria that are synthesising new peptidoglycan
Give two examples of antibiotics that bind to the 30S subunit of prokaryotic ribosomes
- Streptomycin
- Gentamicin
Give an example of antibiotics that bind to the 50S subunit of prokaryotic ribosomes
- Erythromycin
Give two example of antibiotics that are metabolic antagonists
- Sulfonamides
- Trimethoprim
(interfere with enzymes involved in protein synthesis)
Which molecules do sulfonamides compete with to reduce folic acid synthesis in pathogens?
p-aminobenzoic acid (PABA)
What are some examples of points in protein synthesis which antibiotics can inhibit
- Inhibit polymerase (these can be highly toxic)
- Inhibit DNA gyrase (quinolones)
- Block transcription
Which class of antibiotics are less selective than the rest with their toxicity?
- Nucleic acid synthesis inhibitors
- Not as selectively toxic since nucleic acid synthesis is similar between eukaryotes and prokaryotes
