Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis.
The bacterial pathogen Vibrio parahaemolyticus utilizes a type III secretion system to cause death of host cells within hours of infection. We report that cell death is completely independent of apoptosis and occurs by a mechanism in which injection of multiple type III effectors causes induction of autophagy, cell rounding, and the subsequent release of cellular contents. Autophagy is detected by the appearance of lipidated light chain 3 (LC3) and by increases in punctae and vacuole formation. Electron microscopy reveals the production of early autophagic vesicles during infection. Consistent with phosphoinositide 3 (PI3) kinase playing a role in autophagy, treatment of infected cells with a PI3 kinase inhibitor attenuates autophagy in infected cells. Because many effectors are injected during a V. parahaemolyticus infection, it is not surprising that the presence of a sole PI3 kinase inhibitor does not prevent inevitable host-cell death. Our studies reveal an infection paradigm whereby an extracellular pathogen uses its type III secretion system to cause at least three parallel events that eventually result in the proinflammatory death of an infected host cell.
Burdette
Dara L
DL
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yarbrough
Melanie L
ML
Orvedahl
Anthony
A
Gilpin
Christopher J
CJ
Orth
Kim
K
D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D048430:Cell Shape; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages; D051379:Mice; D008854:Microscopy, Electron; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014735:Vibrio Infections / Q000209:etiology / Q000473:pathology; D014736:Vibrio parahaemolyticus / Q000472:pathogenicity*
D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors