Vibrio parahaemolyticus is a Gram-negative bacterium commonly found in marine and estuarine environments. Infection typically results from consumption of contaminated shellfish and leads to acute gastroenteritis. Individuals who are immunocompromised or burdened with pre-existing health conditions are at high risk for severe, potentially lethal complications.
Genomic sequencing of Vibrio parahaemolyticus revealed the existence of two pathogenicity islands that encode both a type III secretion system (T3SS) and putative effectors. The first pathogenicity island contains T3SS1 and is associated with cytotoxicity. We have demonstrated that the V. parahaemolyticus uses T3SS1 and four effectors to orchestrate a host cell death in 3 hours by induction of autophagy, cell bebbling, cell rounding and then cell lysis.
Autophagy is marked by lipidation of the microtubule-associated protein light chain 3, an increase in punctae and vacuole formation. Electron microscopy reveals the production of early autophagic vesicles during infection.
We observed that the deletion of one effector, VopQ, completely abolished the ability of V.para. to induce autophagy in infected cells, although the infected cells still die as a result of translocation of other effectors. Using electron-microscopy, we showed that deletion of VopQ causes internalization of the otherwise extracellular pathogen (Burdette et al., Mol Microbiol 2009). The molecular mechanism used by VopQ to induce autophagy is currently under investigation.
After V. para. induces autophagy, it causes the actin cytoskeleton to collapse and the infected cells round in a synchronized fashion. Recently, we attributed the cell rounding phenotype to VopS, an effector that AMPylates the Rho family of GTPases thereby preventing them from interacting with downstream signaling molecules (Yarbrough et al., Science 2009).
Another T3SS1 effector secreted by V. para. is VPA0450. This effector has been shown to induce membrane blebbing and facilitate host cell lysis. The molecular mechanism used by VPA0450 to induce blebbing and delayed lysis is due to its inositol polyphosphate 5-phosphatase activity that disrupts the dynamic interaction of the cell membrane with the actin cytoskeleton (Broberg et al., Science 2010).
Many other effectors are thought to contribute to V. para.-mediated cell death and future investigations will be directed at understanding the molecular mechanisms they employ to disrupt host cell signaling and promote the spread of infection.