Bacterial pathogens Flashcards
What are commensal bacteria?
Potential? How can this cause disease?
Obligate?
What are the issues with TB?
How can TB be improved?
Bacteria that are not pathogenic
Potentially pathogenic.
- entering tissues where don’t normally reside
- come into contact with immune compromised patients
- acquire virulence factors
Always pathogenic- their lifestyle causes disease
Vaccine is 100 years old- most people die vaccinated as waynes over time. Mtb evolved resistant to every Tb drug. Takes 15,000 pills & 2 years treat MDR-TB
Diagnostics- track and trace
Vaccines
Drugs
Understand MTB better
What are pathogens virulence factors used for?
What are the 4 key events of infection?
What is an extracellular pathogen?
What is the difference between facultative intracellular and obligate intracellular pathogens?
Overpower host defences & to get access to nutrient-rich environments
- Colonisation (invasion & stable adhesion for entry to host cells)
- Multiplication (evade/survive host defence mechanisms & spread locally to distal sites)
- Transmission (exit primary host & enter new host)
- Damage (host damage with direct toxins, invasion, indirect host response)
Doesn’t invade cells but proliferates in extracellular space
Facultative = invade host cells if gives selective advantage (nutrients/lack competition) Obligate = cannot live outside of host cells
How are persisters phenotypically drug tolerant?
Why are they difficult to treat with standard drugs?
What are latent infections?
What is a persistent infection?
Enter dormancy/non-replicating form
Standard drugs target growth mechanism- in dormancy they are not growing/replicating
Infections where pathogen doesn’t cause active disease unless reactivated (usually dormant/hidden)
Slow burning but progressing VIRAL infection (not bacteria)
Who’s postulates are key to know whether a pathogen causes disease? (there are exceptions & limitations)
What are the 4 ideas?
Koch’s postulates
- Pathogen must be present in every case disease
- Pathogen must be isolate from diseased host & grown in pure culture
- Disease must be reproduced when pure culture is inoculated in healthy host
- Pathogen must be recoverable from experimental infected host
How do bacteria colonise their hosts? What are the 4 key ideas and examples.
Are virulence factors continuously expressed?
What are the main characteristics of virulence factors?
- Motility (finding right location e.g open wound, chemotaxis, migration, surface flagella)
- Adhesion (attach stably to surface on host cells or matrix- acquired by secretion systems with pili)
- Invasion (enter host cell/tissue & cell to cell spread)
- Replication (growth, host defence evasion & tissue destruction)
No- regulated in response to host environment- co regulated by signals & transduction systems in global regulation
Specialised (based on host environment)
Genetic context- can be on plasmids or bacteriophages & can be grouped in pathogenicity islands on chromosome
Function- secreted onto bacterial cell surface & facilitate host interaction. Sometimes lead host cell destruction & release toxins that interfere with host cell interactions
How do bacteria colonise their hosts? What are the 4 key ideas and examples.
Are virulence factors continuously expressed?
What are the main characteristics of virulence factors?
- Motility (finding right location e.g open wound, chemotaxis, migration, surface flagella)
- Adhesion (attach stably to surface on host cells or matrix- acquired by secretion systems with pili)
- Invasion (enter host cell/tissue & cell to cell spread)
- Replication (growth, host defence evasion & tissue destruction)
No- regulated in response to host environment- co regulated by signals & transduction systems in global regulation
Specialised (based on host environment)
Genetic context- can be on plasmids or bacteriophages & can be grouped in pathogenicity islands on chromosome
Function- secreted onto bacterial cell surface & facilitate host interaction. Sometimes lead host cell destruction & release toxins that interfere with host cell interactions
What is a biofilm? How does this affect infections?
How do enteropathogenic E coli adhere to host cells?
How are these structures formed?
Complex matrix on host tissues- infections difficult to eradicate by immune system & antibiotics
Build pedestals made of host material
T3SS is upregulated & forms a translocon. Effectors sent into host cells via translocon & Ec Tir inserts into host membrane & interacts with Ec Intimin on bacterial surface. This promotes Tir clustering- host actin is remodelled to form pedestals
Bacteria invade cells by being internalised by host cell. What are the 2 ways of internalisation?
What do bacteria do after invasion?
What happens to some of the bacteria?
What is required for the bacteria to move intracellularly?
Zipper mechanism = receptor mediated endocytosis
Trigger mechanism = bacterial proteins injected via T3SS leading to actin remodelling
Spread through epithelial cell layer to move intracellularly, to replicate & to spread
Escape from entry vacuole into cytosol
Host cytoskeleton
What are vacuoles used for by bacteria?
How else can bacteria survive in host cells?
Use to shield themselves from host defences & survive & replicate in there
- Survive in macrophages to spread locally & in body & fight host defence system
- Inhibit phagocytosis by inhibiting fusion of phago-lysosome or inhibit reduction in pH required for enzymes
- Survive oxidative burst (escape late endosome)
Hosts hide iron, so how do pathogens scavenge iron?
How do pathogens bypass the low pH in stomach?
How do pathogens bypass macrophages?
How can pathogens resist phagocytosis?
Use proteins with high affinity for iron- secreted out of the bacteria & re-import into bacteria with iron bound to them
Resist low pH by pumping H+ out of cells
Paralyse them by disrupting their signalling & trafficking by injecting effector proteins into the host cell
Made capsules with polysaccharide & can also mimic host cells to avoid detection- shield in this capsules
Direct damage mechanisms to host cells:
What do cytolysins do when secreted?
What do phospholipases do?
Enzymatic exotoxins?
Toxins- form holes in membrane
Phospholipase degrade phospholipids in membrane
Enter host cells with receptor-mediated endocytosis/retrograde transport & alter catalytic activity
What 4 pathways/substrates do enzymatic cytotoxins target?
What is retrograde transport system?
ADP-ribosylating enzymes
Mimicry of host adenylate cyclase
N-glycosidation
Cleave host SNAREs (interfere with neurotransmitters)
Toxin enters endosome, golgi & then ER to be further distributed
How is indirect damage caused?
What are the 2 examples?
How do granuloma actually spread disease?
What are the 2 methods for bacteria to evade recognition by antibodies?
How can bacteria inactivate antibodies?
By the host’s response to bacteria
Acute inflammation (response to alarm signals- can be serious) Chronic inflammation (uncommon)
Can hire immune cells- infect some of them & be transported to other locations in body
- Phase variation- complex DNA rearrangement mechanisms
- Antigenetic variation- shut off/switch expression of surface proteins
specific proteases cleave antibodies- bacteria directly bind
What does adhesion & invasion involve?
How are bacteria taken in with this material & host cell entry?
How can this material help bacteria mobility?
How can you define a virulence factor?
What is the early view of bacterial virulence?
What is the continuous arms race?
Host actin
Host actin envelopes the bacteria (zipper, trigger, phagocytosis)
Makes actin tails- move around cell & also out (escape dissemination)
Delete gene- shows loss of virulence in model system- add gene back to restore virulence- find out what it does
- not the only virulence factor
Vaccination with inactivated toxins = less bacterial infection, and only have 1 toxin to cause disease (wrong)
that hosts and pathogens co-evolve together (new defence comes new method of attack)
listeria monocytogenes is pathogenic but only at a high temperature- how?
clouds started to form around L.monocytogenes- what happened to them when they were decorated with myosin?
what happened after cytochalasin D treatment?
what are these?
where is it in the bacteria?
virulence genes switched on at high temp by RNA thermometer- which melts RNA & becomes accessible for ribosome binding & expression of virulence genes
clouds condensed
inhibits actin polymerisation- so bacteria no longer dispersed
actin
actin tails/comets
