Bacterial Pathogenesis, Survival, Processes, and Environmental Interactions Flashcards
How do commensal bacteria on our bodies protect against pathogens?
outcompete pathogens for nutrients
take up space
produce antimicrobial compounds
Colonisation of commensals in newborns acts as stimulus for immune system development
What is an opportunistic pathogen?
an otherwise harmless bacteria that can cause infections in individuals w abnormal host defences
or when in the right conditions
eg commensals in our gut can be harmful if exposed in other places
Name and define the different types of toxins produced by bacteria.
exotoxins: any toxin that is actively secreted by a bacterium in the environment or supernatant
endotoxin: a synonym for the LPS of gram-negative bacteria (cell-surface bound)
enterotoxin: an exotoxin that is effective in the gastrointestinal tract
Why must bacteria sequester iron?
iron is an essential nutrient for most bacteria
limiting in host
sequestration is critical for in vivo success
performed by iron binding components called siderophores
Increased siderophores can lead to higher virulence as iron is needed for toxin production/gene regulation (or at least my notes say so 🐮)
How does cholera cause disease?
attaches to ganglioside receptors in the gut
leads to mass amount of cAMP production which causes inhibition of reabsorption of Na and K as well as hypersecretion of Cl- ions
toxins don’t cause physical damage, purely chemical
How does shigella cause disease?
able to bypass stomach as it encodes genes that allow it to overcome the acidic environment allowing it to reach the small gut
once it reaches it, releases toxins that cause pathological damage
taken up by microfold cells (m cells) in the small gut and cause them to apoptose
Can also disseminate from gut and cause damage in the CNS and kidney (also sepsis)
What is a Type III Excretion System (T3SS)?
an injection system that forms a channel for toxins to enter from microbe into host
is a virulence factor
allows pathogenesis
Spans multiple membranes
How is the genetic shift of Yersinia pestis (the cause of the bubonic plague) activated
temperature shift from flea to human
What are some common themes of pathogenesis?
- breach of epithelial barrer
- proliferation intraphagosomally
- toxin release and delivery via T3SS
evasion of immune system by alteration of LPS structure and delivery of effectors via T3SS
What is the Sec pathway?
is used to export unfolded proteins in gram- bacteria
unfolded proteins move into periplasmic space where they are packaged by proteins in outer membranes
involves the proteins; SecA, SecYEG, SecB
What is the TAT pathway?
is used to export folded proteins in gram- bacteria
3 components:
- Tat A: formation of membrane forming channel
- TatB: signal peptide binding
- TatC: signal peptide binding, recruits TatA
transported protein into periplasm or extracellularly by T2SS
How does a Type I Secretion System work?
pulls membranes together allowing a channel to form
major efflux pump
Operates on proteins
What is the role of a Type IV Secretion System?
moves genetic material between microbes
What is a regulator?
usually a specific DNA binding protein that
binds in control region
Either stabilises RNA pol-promoter interaction (on) or competes for space with RNA pol (off)
What is a regulon?
a group of genes controlled by a common regulator
How many pathogens is enough to start an infection?
100
(Seems quite vague but whatever the lecture says ig 🐮)
(Wasn’t there another one that only took a few to cause disease - 🦑
(Probably 🐮)
Dangers of commensals?
If displaced can cause infections
Antibiotic dysbiosis (Clostridium)
Can convert commonly ingested food substances into carcinogens
Immunocomprimised hosts
What is the range of pathogenisis?
Pathogenic: can cause disease in individuals with normal host defences
Non-pathogenic: invade with no obvious detectable symptoms
Asymptomatic: detected by presence of organisms or antibodies raised against them
Latency: some organisms remain latent until activated with recurrence if symptoms
Opportunistic: can cause disease under specific conditions
What is a commensal?
An organism found normally on parts of body that are exposed to or communicate with the external environment
(but da gut bacteria - 🦑)
(The gut is external 🐮)
How can bacteria which are part of normal flora become pathogenic?
They acquire extra virulence factors (from plasmids)
What can change the normal flora?
Changes in physiology during development
Antibiotics selecting for antibiotic resistant strains in body - overgrowth of said strain
New organisms acquired (eg newborn gains flora from maternal genital tract)
Harmful effect of flora alteration by antibiotics?
Antibiotic use
Sensitive gut flora killed
Overgrowth of resistant flora, eg C. difficile
C. difficile toxin production
Diarrhoea, pseudomembraneous colitis
What are Koch’s postulates?
Used to figure out if a given pathogen causes a specific disease
-Pathogen must be present in any case of the disease
-Pathogen must be isolated from diseased host and grown in pure culture
-Specific disease must be reproduced when pure culture is inoculated into healthy susceptible host
-pathogen must be recoverable from experimentally infected host
What are fimbriae?
Adhesion structures on gram-negative bacteria
Made up of various protein subunits
Interact with eukaryotic cells/inert surfaces via receptors at tip (many of which recognise sugars)
What are Pili?
Structurally similar to fimbriae, except longer
Most of the time only one is present on the surface
Involved in bacterial coniugation (F-pili), or act as receptors for phages (CTX phage in V. Cholerae)
Purpose of Adhesins?
Adhering to host cells
Formation of colonies and biofilms
Purpose of bacterial toxins?
One use is to destroy tissue
Purpose of invasins?
Invading and multiplying in host cell
How does Botulinum toxin work?
Clostridium botulinum releases toxin
Botulinum toxin acts at motor end plate to prevent acetylcholine release from vesicles
Causes lack of stimulus to muscle fibres -> irreversible relaxation and flaccid paralysis of muscles
How does tetanus toxin work?
Clostridium tetani releases toxin
Toxin binds to inhibitory inter neurons and prevents the release of glycine (which under normal conditions acts on motor neurons to block excitation/release of acetylcholine)
Causes irreversible contraction, spastic paralysis
What are invasion factors?
Exoenzymes used to invade host
Proteases, Glycosidases, Nucleases, Lipases
Also have toxins which work physically instead of enzymatically -insert into membrane instead
Defensive pathogenicity factors?
Protect from host defence mechanisms
Negatively charged polysaccharide capsule (protect from phagocytosis and desiccation)
Slime
Biofilm (protects inner core from attack by immune system/antibiotics)
Type II secretion system?
Moves protein into the periplasm via the sec and TAT systems
How does the body tell pathogenic and commensal E. Coli apart?
T3SS present only in pathogenic (used for translocation of effector molecules) is sensed by intestinal cells (T3SS also trigger immune response)
Commensals don’t have the genes encoding T3SS or toxins
Therefore genomic variation dictates host-pathogen interactions
What is the arn operon?
Controlled by PhoPQ TCS
Alters bacteria’s LPS so they can’t be sensed by the host immune system (immune evasion)
Also encodes resistance to anti microbial molecules released by innate cells
Quorum sensing?
Gram negative release Acyl-homoserine lactones
Gram positive release Autoinducing peptides
(Produced by QS signal synthases)
More bacteria = higher QS molecule concentration
Sensed by TCS, cause changes in gene expression at a certain threshold of bacteria
(Eg turning on virulence genes when a sufficient amount of bacteria to overwhelm immune system is present)
