A Vibrio parahaemolyticus T3SS Effector Mediates Pathogenesis by Independently Enabling Intestinal Colonization and Inhibiting TAK1 Activation

Abstract

SUMMARY Vibrio parahaemolyticus type III secretion system 2 (T3SS2) is essential for the organism’s virulence, but the effectors required for intestinal colonization and induction of diarrhea by this pathogen have not been identified. Here, we identify a type III secretion system (T3SS2)-secreted effector, VopZ, that is essential for V. parahaemolyticus pathogenicity. VopZ plays distinct, genetically separable roles in enabling intestinal colonization and diarrheagenesis. Truncation of VopZ prevents V. parahaemolyticus colonization, whereas deletion of VopZ amino acids 38–62 abrogates V. parahaemolyticus-induced diarrhea and intestinal pathology but does not impair colonization. VopZ inhibits activation of the kinase TAK1 and thereby prevents the activation of MAPK and NF-κB signaling pathways, which lie downstream. In contrast, the VopZ internal deletion mutant cannot counter the activation of pathways regulated by TAK1. Collectively, our findings suggest that VopZ’s inhibition of TAK1 is critical for V. parahaemolyticus to induce diarrhea and intestinal pathology.

Type Three Secretion System Island-Encoded Proteins Required for Colonization by Non-O1/Non-O139 Serogroup Vibrio cholerae

“…A recently identified effector in V. parahaemolyticus, named VopZ (distinct from the VopZ protein described here), was shown to play a role in colonization (13). We have identified a homologous protein encoded by the AM-19226 T3SS genomic island at the junction of the 5=-flanking sequences and the central region, but its role in strain AM-19226 colonization remains to be tested.…”

“…T3SS2 is associated with pandemic V. parahaemolyticus strains, whereas T3SS1 is present in all strains (11). Comparison of the T3SS genomic islands in V. cholerae strain AM-19226 and V. parahaemolyticus strain RIMD2210633 reveals synteny within a conserved, central "core" region, flanked by 5= and 3= regions of greater coding diversity between clades and species (4,10,(12)(13)(14). The core region encodes proteins that form the T3SS structural apparatus and is transcriptionally organized into four main operons in V. cholerae ( Fig.…”

Subversion of MAPK signaling by pathogenic bacteria

“…It is unclear whether VopZ acts directly on TAK1, and its enzymatic activity has yet to be uncovered. 22 Pseudomonas syringae tightly regulate the plant MAPK Pseudomonas syringae (P. syringae) is a gram-negative plant pathogen that causes a wide variety of diseases, including blights, leaf spots, and galls in different plant species. 49 To facilitate stable infection, P. syringae subvert MAPK signaling via T3SS effectors HopAI1 and HopF2 (Figure 2).…”

Virulence gene expression of Vibrio parahaemolyticus in the viable but nonculturable state

“…T3SS is thought to be triggered when the bacteria come in close contact with the host. Effector proteins, such as VopT (involved in cytotoxicity) and VopZ (enables intestinal colonization and diarrheagenesis) are injected directly into host cells via its needle-like structures spanning the bacterial inner and outer membrane (Kumar et al, 2014;Zhou et al, 2013). T3SS is found in both chromosomes of V. parahaemolyticus: abbreviated as T3SS1 (on chromosome 1) and T3SS2 (on chromosome 2) (Makino et al, 2003).…”

“…Therefore the presence of T3SS2 is strongly related to the pathogenicity of V. parahaemolyticus to humans. T3SS2 promotes bacterial cell invasion, inactivation of the host immune pathway, and disruption of the gut epithelial barrier (Ritchie et al, 2012;Zhang et al, 2012;Zhou et al, 2013), resulting in enterotoxicity in infant rabbit models (Ritchie et al, 2012). T3SS1 is associated with killing host cells through autophagy, membrane blebbing, and finally cell lysis (Burdette et al, 2008).…”