Arp2/3-independent assembly of actin by Vibrio type III effector VopL

Abstract

Microbial pathogens use a variety of mechanisms to disrupt the actin cytoskeleton during infection. Vibrio parahaemolyticus (V. para) is a Gram-negative bacterium that causes gastroenteritis, and new pandemic strains are emerging throughout the world. Analysis of the V. para genome revealed a type III secretion system effector, VopL, encoding three Wiskott-Aldrich homology 2 domains that are interspersed with three proline-rich motifs. Infection of HeLa cells with V. para induces the formation of long actin fibers in a VopL-dependent manner. Transfection of VopL promotes the assembly of actin stress fibers. In vitro, recombinant VopL potently induces assembly of actin filaments that grow at their barbed ends, independent of eukaryotic factors. Vibrio VopL is predicted to be a bacterial virulence factor that disrupts actin homeostasis during an enteric infection of the host.actin assembly ͉ microbial pathogenesis ͉ virulence ͉ stress fibers ͉ WH2 domains

Regulation of type III secretion system 1 gene expression inVibrio parahaemolyticusis dependent on interactions between ExsA, ExsC, and ExsD

“…36 VopL (Vpa1370) is secreted by T3SS2 of V. parahaemolyticus and it induces formation of long actin stress fibers resulting in the disruption of actin homeostasis. 35 Expression of T3SSs in Gram-negative bacteria is controlled by specific environmental conditions that trigger activity from specific transcriptional regulators. 38,39 For example, the central regulator, HilA, controls expression of SPI1 in Salmonella by directly binding to the promoters of prg/org and inv/spa operons.…”

“…29,30,[32][33][34][35][36] For example, VopS (Vp1686) is secreted 29 and translocated 33,37 into host cells by T3SS1 where it inhibits Rho GTPase 37 and NFkappaB activity, 30 leading to depolymerization of actin structure 37 and apoptosis, 30 respectively. Further studies show that VopS (Vp1686) inhibits Rho GTPase activity by modifying a conserved residue with AMP.…”

WASH and WAVE actin regulators of the Wiskott–Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes

“…We tested whether FAM21 functions similarly using the pyrene-actin polymerization assay and the Vibrio type III effector VopL (25), which potently enhances actin assembly (Fig. 4B).…”

Diarrhea induced by infection of <I>Vibrio parahaemolyticus</I>

“…In addition, VopT is partially responsible for the T3SS2-dependent cytotoxicity observed in Caco-2 cells (34). VopL (VPA1370), which has three Wiskott-Aldrich homology 2 domains, potently and directly facilitates the assembly of actin without any other eukaryotic factors (35). VopC (VPA1321) exhibits 38% homology to Escherichia coli cytotoxic necrotizing factor (34).…”