Inhibition of MAPK Signaling Pathways by VopA from Vibrio parahaemolyticus

Abstract

During infection, bacterial pathogens utilize a type III secretion system to inject effectors into the cytoplasm of a target cell where they disrupt the defense system of the host cell. Vibrio parahaemolyticus, a causative agent of gastroenteritis endemic in Southeast Asia, has a type III secretion system that encodes a novel member of the YopJ-like protein effector family, VopA (Vibrio outer protein A). Our studies revealed that Vibrio VopA encodes an evolutionarily conserved activity that is extremely potent and requires an intact catalytic site to abrogate signaling pathways in a manner distinct from that of other YopJ-like effectors. We observed that VopA efficiently inhibits the MAPK signaling pathways but not the NFB pathway in mammalian cells. When expressed in yeast, VopA induces a growth arrest phenotype and also blocks yeast MAPK signaling pathways. Our observations provide insight into the immense diversity of targets utilized by YopJ-like effectors to manipulate eukaryotic signaling machineries that are important for the response and survival of the host cell during infection and/or symbiosis.

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

“…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.…”

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

“…The first effector that we characterized, VopA, was identified as a YopJ-like protein and, subsequently, was shown to inhibit MAPK signaling pathways (19). Another gene, VopL (Vibrio outer protein L, VPA1370, 483 aa), was also identified as a candidate TTSS2 effector protein.…”

Inhibition of Cdc42-dependent signalling in Saccharomyces cerevisiae by phosphatase-dead SigD/SopB from Salmonella typhimurium

“…This implies that phosphatasedead SigD expressed in yeast is able to complex with both Cdc24 and Cdc42. example, YopE, YopJ and YopM from Yersinia (Von PawelRammingen et al, 2000;Lesser & Miller, 2001;Yoon et al, 2003;Skrzypek et al, 2003), SopE2 and SptP from Salmonella (Rodríguez-Pachó n et al, 2002), effectors encoded by the LEE pathogenicity island from enteropathogenic E. coli (EPEC; Rodríguez-Escudero et al, 2005a) as well as proteins from Vibrio and Pseudomonas (Rabin & Hauser, 2003;Sato et al, 2003;Trosky et al, 2004) have been expressed in yeast. The pros and cons of the yeast system for studying virulence factors have been recently discussed by Valdivia (2004).…”