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Flashcards in Type III Secretion Systems Deck (24):

what are the General Pathways for Secretion of Proteins in Bacteria?

1. General secretory pathway (Sec) across cytoplasmic membrane
2. Twin arginine (Tat) translocation – Across plasma membrane into periplasm or extracellular matrix.
- Uses signal sequence (S- R-R-x-F-L-K) in N-terminal region. - Translocates folded proteins using proton motive force.


What are the functions of bacterial secreted proteins?

Immune modulators
Modulation of host membranes


what are the two types of Sec-Dependent Secretion Pathways?

1. Type II secretion (2-step)

2. Type V (autotransporters)


what are the Sec-Independent Secretion Pathways?

1. Type I secretion (ABC transporters)
2. Type III secretion (contact-dependent)
3. Type IV secretion (conjugal transfer)
4. Type VI secretion
5. Type VII secretion


how are proteins secreted from bacteria?

1. General secretory pathway (Sec) across cytoplasmic membrane – Gram positive & negative
2. Co-translational translocation of membrane proteins and proteins with very hydrophobic signal sequences.
- Signal recognition particle targets ribosome to translocase through FtsY receptor.
3. Type II secretion(2-step)–Gram negative Sec-dependent transport of ‘secretins’ that form outer membrane pore for secretion of pilus components, enzymes, toxins (cholera toxin, exotoxin A, elastase), etc.


Type I secretion(ABCtransporters)–Gram negative

Complex pore crosses both membranes. One group specific for large proteins and second group for small proteins and peptides.


Type IV secretion(conjugaltransfer)–Gram negative

Pilus-like structure for transfer of DNA and proteins to another bacterial cell, to external environment, or to eukaryotic cells


Type III secretion

Gram negative needle-like structure transfer effector proteins to another cell


give 2 Examples of type III secretion systems

1. Yersinia enterocolitica
- Yop – blocks phagocytosis, inhibits inflammatory
2. Pseudomonas aeruginosa
- Psc – cytoxicity, blocks phagoctyosis


name 3 Yersinia species and the diseases they cause.

• Y. pestis – bubonic plague (lymph nodes; tick borne), septicaemic plague (blood and organs; tick borne), pneumonic plague (pulmonary; inhalation)
• Y. enterolitica – enteritis with spread to mesenteric lymph nodes (food/water)
• Y. pseudotuberculosis – mesenteric adenitis with granulomas in lymph nodes (food/water)


what are the Major Yop Effectors?

1. YopH – 468 aa, major effect on pathogenesis, tyrosine phosphatase, inhibits phagocytosis, lysosome maturation, degranulation of neutrophils. Inhibits signaling via chemokines, possibly also B and T cell responses
2. YopM – ~409 aa, reduces pathogenesis, non-enzymatic protein, reduces proinflammatory cytokine release and causes depletion of NK cells
3. YopE – 219 aa, reduces pathogenesis, GTPase activating protein, inhibits non-opsonic phagocytosis and release of proinflammatory


name 3 Minor Yop Effectors

1. YopJ – 288 aa, required for spread of bacteria inside host, cysteine protease inhibits MAPK and NF-kB, causes apoptosis of macrophages and dendritic cells in combination with TLR4 signal, suppresses cytokine release
2. YopO – 730 aa, variable effect on pathogenesis, anti-phagocytic, multifunctional, serine/threonine kinase binds to Rho
3. YopT – 322 aa, no effect on pathogenesis, antiphagocytic, cysteine protease.


whats the prevalence of Diarrhoeal diseases?

• ~2 million deaths per year
• mainly children 50% of deaths due to enteropathogenic E. coli (EPEC)
• survivors may suffer irreversible damage to physical and mental development


effectors encode by Locus of enterocyte effacement (LEE)

biogenesis of the type III secretion system
effector molecule
damages mitochondria
translocated intimin receptor
translocation pore
needle component
disrupts tight junctions


what are the Functions of Pedestals in EPEC system?

1. Improve colonisation efficiency
- actin-based motility
- resistance to detachment
2. Improved translocation of effector proteins
- EspB facilitates disassociation of host cell contacts
-EspF/Map disrupt tight junctions, enter mitochondria and cause apoptosis
-EspF inhibitis phagocytosis
-EspG/EspG2 active the host protease calpain leading to disruption of tight junctions, cell rounding and cell death
3. Inhibition of phagocytosis


Type III Secretion Systems Summary

1. Bacteria (particular Gram -ves) have multiple pathways for secretion of proteins
2. Type III secretion systems are multi-component complexes enabling ‘injection’ of effector proteins into host cells
3. Yersinia use Type III secretion systems to prevent phagocytosis, to inhibit innate immunity and to prevent release of proinflammatory cytokines
4. Enteropathogenic E. coli (EPEC) use a type III secretion system to ‘re-model’ the host cell and mediate intimate attachment and microcolony formation


what are Type V (auto transporters)?

- Gram negative,
- large passenger domain (20-400 kDa)
- C-terminal translocator (~30 kDa).
- Include adhesins (YadA, Hia) and other functions (IgA protease of N. gonorrhoeae).
- Very common (500+ proteins)


how does Type II secretion (2-step) work?

– Gram negative transport of ‘secretins’ form outermembrane pore for secretion of pilus components, enzymes,


how does Type I secretion (ABC transporters) work?

- Gram positive & negative
- Complex pore crosses both membranes


what is Type III secretion (contact-dependent)?

- Gram negative
- Channel across both bacterial membranes,
- injection pore through eukaryotic membrane


Type IV secretion (conjugal transfer)

- Gram positive & negative
- Pilus-like structure for transfer of DNA and proteins to another bacterial cell, to external environment, or to eukaryotic cells


what is Type VI secretion?

- Gram negative
- Phage-tail-spike-like injectisome similar to Type III & IV
- Present in a quarter of proteobacteria and required for virulence in both human and animal pathogens.
- Involved in delivery of effector proteins


how does Type VII secretion work?

– Gram positive (mycobacterium)
- Integral inner membrane channel linked to separate channel in mycomembrane.
- Effectors secreted as heterodimers with chaperone


how do the Yersinia cause disease?

1. Disseminate in macrophages during early stages
2. becomes resistant to phagocytosis in late stages
3. Virulence factors YadA (an adhesin), an invasin and the Yop T3SS located on plasmid
4. Proinflammatory cytokines (IFNg gamma and TNFa) protect against Yersinia infections