Lecture 7 - Bacterial Effector Proteins Flashcards
Bacterial effector proteins are a specialized class of ______ factors.
L. Pneumophila and S. Enterica rely heavily on effector proteins for ______.
Virulence
Infection
What are the 4 stages of infection?
1) Exposure to pathogen
2) Adherence to skin/mucosa
3) Invasion through epithelium
4) Colonization and growth
this leads to toxicity and invasiveness, causing tissue damage and disease.
Which statement is true regarding virulence factors?
1) Production of virulence factors occurs during the Colonization and Growth stage.
2) Virulence factors function by interacting with the host; often modify host function for the benefit of pathogen.
3) Expression is static; same virulence factors are made at different timepoints of infection.
2!
1) Production of virulence factors occurs during ALL FOUR STAGES OF INFECTION (entire course)!
3) Expression is DYNAMIC; different virulence factors are made at different timepoints of infection for different purposes. Effectors made immediately after infection are often different than those made during late infection.
*VFs are complex
*bacteria have evolved clever ways to take advantage of the host
Bacteria can establish infection using diverse strategies.
What are the three typical strategies used by pathogens?
1) Extracellular
2) Intracellular (vacuoles): remain in compartments
3) Intracellular (cytosolic): break free from compartments
*all secrete virulence proteins to mediate infection
Intracellular bacteria are first internalized into ___________.
Compartments
*can either remain or break free
Why are the most successful virulence factors often not the most toxic?
Bacterial infection is a SYMBIOTIC RELATIONSHIP.
Successful pathogens balance host damage and host.
Pathogens need to MANIPULATE THE HOST to establish infection (to benefit the pathogen). But host death would lead to END OF INFECTION; therefore an INTRICATE BALANCE is needed!
What are the two major pathogenesis tool used to cause infection by pathogens?
1) Toxins (endo and exotoxins)
2) Other virulence proteins -> effectors
Endotoxins are normal constituents of ______?
When are they active?
Compared to exotoxins:
They exhibit relatively _____ toxicity. They exhibit more ______ effects.
Bacterial cell wall (LPS)
They are active only after released: during CELL DIVISION or bacterial CELL LYSIS.
low (but can be fatal at high doses); non-specific effects (fever, aches, shock)
Exotoxins are synthesized and ______ by the pathogen.
What is their molecular structure?
What do they do?
Secreted
Protein
Cause damage to host cells
Which statement regarding exotoxin is false?
1) Exotoxins have limited diversity in structures.
2) A pathogen may secrete more than one different toxin.
3) They are susceptible to antibodies; therefore highly immunogenic (robust immune response).
1!
Exotoxins have DIVERSE structures.
How are effectors same as toxins?
How do they differ from toxins?
Like toxins, effectors are SECRETED.
UNLIKE toxins, effectors MANIPULATE host pathways to mediate infection.
UNLIKE toxins, they are usually NOT OVERLY toxic!
Bacterial effectors are specialized virulence proteins that are ______ into host cells using specialized bacterial ______ _____.
They function to manipulate host cell pathways to facilitate infection. They evolved to function in the ____ cell not the _____ cell.
Injected; Secretion Systems
host; bacterial
Which SS does Salmonella use to infect host cells?
T3SS
How do bacterial effectors function at a molecular level?
They usually target a host protein or protein complex; host pathogen protein-protein interaction ALTERS function of HOST PROTEIN.
The legionella effector ____ targets host regulatory GTPase _____.
SidM; Rab1
Effectors target _____ _____ processes.
Effectors are often _________ (ex, several co-evolve to target different host proteins in ____ pathway).
Effectors can also have ____ mechanisms. Give examples.
Diverse cellular
Co-operative; same
Complex
- some can MIMIC MAMMALIAN proteins to manipulate host cell processes
- some can have ENZYMATIC ACTIVITY on host proteins
- some can have MULTIPLE DOMAINS with different functions
What is the general purpose of effectors?
Usually, to aid bacterial survival and/or replication in the host, without causing death.
What are effectors being used in:
1) Salmonella
2) Listeria
Salmonella uses effectors for INVASION in many different types of cells for infection. They turn on uptake process in cells that are normally off (for example epithelial cells).
Listeria uses a SINGLE effector to POLYMERIZE HOST ACTIN to give it MOTILITY (for replication and spread). The effector mimics a mammalian protein that polymerizes actin.
Are bacterial effectors just important in human infection? If not, give examples.
No! They are important for infection of PLANTS and ANIMALS too.
P. syringae infects agriculturally important crops such as tomato, tobacco, and beans. Effectors help EVADE host immunity.
Pathogenic E. coli strains cause respiratory and reproductive diseases in chickens, pigs and cows. Effectors help mediate infection.
(T/F) Effectors sole role lies in infection.
False!
Effectors play important roles OUTSIDE infection. They help mediate SYMBIOTIC RELATIONSHIPS between organisms.
Root nodules are important for nitrogen fixation in legumes. Some nitrogen-fixing bacteria use effectors to promote Nodulation.
T6SS effectors often play roles in killing competing microbes in MICROBIAL COMPETITION.
What are some examples of targets of effector proteins in host cells?
Bacterial effectors target diverse cell processes.
1) Tight junctions
2) Cytoskeleton
3) Cellular defense pathways (endocytic, autophagy, immune cell function)
4) Biochemical activities
5) Protein degradation (proteasome)
6) Organelle function
1) What are small GTPases? What do they help define and what does this allow for?
2) Small GTPases are subclassified into 5 families. What are they?
3) What do the GTPases that belong to the Ras superfamily control?
4) Which families of GTPases are most targeted by effectors?
1) Small GTPases are regulatory proteins often targeted by effector proteins. Within host cells, compartment membranes have UNIQUE GTPase compositions; this helps define their MEMBRANE IDENTITY. This allows researchers to identify and study them.
2) Ras, Rab, Rho, Arf, and Ran. There’s over 150 members.
3) Control important host cell processes that include RESPONSE PATHWAYS to infection, INTRACELLULAR TRAFFICKING, and CYTOSKELETAL REORGANIZATION.
4) Effectors can target all 5 families of GTPases but Ras superfamily are frequently targeted by bacterial effectors to mediate infection.
How do host Ras-superfamily GTPases work?
Ras-superfamily GTPases are small G-proteins that function as MOLECULAR SWITCHES for signaling pathways.
They cycle between active (GTP-bound) and inactive (GDP-bound) forms on biological membranes.
When active, they interact with HOST BINDING partners to mediate cellular effectors.
GTPases are fine tuned in the host using regulatory proteins. What are the two main regulatory proteins?
1) GEF (guanine nucleotide exchange factor) –> activate
2) GAP (GTPase activating protein enzyme) –> deactivate
Membrane lipids such as __________ are important to organelle function.
Intracellular compartments have ____ membrane lipid compositions; this helps define __________ ______.
Phosphoinosides (PIs)
Unique; membrane identify
*bacterial effectors often bind or manipulate processes that involve membrane lipids
Within host cells, PIs can recruit host proteins to mediate specific functions.
What are these functions?
1) Organelle trafficking
2) Secretion
3) Compartment fusion
