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

Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 11/2007; 104(43):17117-22. DOI: 10.1073/pnas.0703196104
Source: PubMed

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.

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Available from: Dara L Burdette, Aug 31, 2015
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    • "(Makino et al., 2003), which blocks the MAPKs signaling pathway by inhibiting the start and biological activity of mitogen-activated protein kinase (Trosky et al., 2004), thereby suppressing cell division via a new mechanism. Vop L (VPA1370) contains three Wiskott Aldrich homology 2 (WH2) domains and a C-terminal domain (VCD; Namgoong et al., 2011; Yu et al., 2011), which generally induces the formation of polarized actin fibers and accelerates the gathering of actin filaments by binding to actin monomers (Liverman et al., 2007). Notably, Vop L may provide a favorable microenvironment in which bacteria can replicate, thereby enhancing the uptake and invasion of V. parahaemolyticus. "
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    ABSTRACT: Vibrio parahaemolyticus, a Gram-negative motile bacterium that inhabits marine and estuarine environments throughout the world, is a major food-borne pathogen that causes life-threatening diseases in humans after the consumption of raw or undercooked seafood. The global occurrence of V. parahaemolyticus accentuates the importance of investigating its virulence factors and their effects on the human host. This review describes the virulence factors of V. parahaemolyticus reported to date, including hemolysin, urease, two type III secretion systems and two type VI secretion systems, which both cause both cytotoxicity in cultured cells and enterotoxicity in animal models. We describe various types of detection methods, based on virulence factors, that are used for quantitative detection of V. parahaemolyticus in seafood. We also discuss some useful preventive measures and therapeutic strategies for the diseases mediated by V. parahaemolyticus, which can reduce, to some extent, the damage to humans and aquatic animals attributable to V. parahaemolyticus. This review extends our understanding of the pathogenic mechanisms of V. parahaemolyticus mediated by virulence factors and the diseases it causes in its human host. It should provide new insights for the diagnosis, treatment, and prevention of V. parahaemolyticus infection.
    Frontiers in Microbiology 03/2015; 6:144. DOI:10.3389/fmicb.2015.00144 · 3.94 Impact Factor
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    • "The tandem WH2 array of VopL is a weak actin nucleator on its own; nucleation activity is improved through VopL dimerization, which is mediated by the effector's C-terminal domain (Yu et al., 2011). Cell expression of VopL causes a dramatic actin phenotype characterized by formation of stress fibres that span the whole cell body (Liverman et al., 2007) (Fig. 3). Stress fibres exert tension that allows cell reshaping; this may prove beneficial for bacterial entry or for maintenance of cell structure during bacterial replication. "
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    ABSTRACT: Entry into host cells and intracellular persistence by invasive bacteria are tightly coupled to the ability of the bacterium to disrupt the eukaryotic cytoskeletal machinery. Herein we review the main strategies used by three intracellular pathogens to harness key modulators of the cytoskeleton. Two of these bacteria, namely Listeria monocytogenes and Salmonella enterica serovar Typhimurium, exhibit quite distinct intracellular lifestyles, and therefore, provide a comprehensive panel for the understanding of the intricate bacteria-cytoskeleton interplay during infections. The emerging intracellular pathogen Vibrio parahaemolyticus is depicted as a developing model for the uncovering of novel mechanisms used to hijack the cytoskeleton. This article is protected by copyright. All rights reserved.
    Cellular Microbiology 12/2014; 17(2). DOI:10.1111/cmi.12399 · 4.82 Impact Factor
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    • "VopA and VopZ both target cellular immunity by inhibiting different components of the MAPK pathway [12], [15]. VopT ADP-ribosylates Ras, and the three other effectors, VopC, VopL, and VopV, alter actin dynamics [13], [16], [17]. Notably, VopC constitutively activates Cdc42 through a deamidation reaction to promote invasion of the bacterium into non-phagocytic cells [13], [18]. "
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    ABSTRACT: Vibrio parahaemolyticus is a Gram-negative halophilic bacterium and one of the leading causes of food-borne gastroenteritis. Its genome harbors two Type III Secretion Systems (T3SS1 and T3SS2), but only T3SS2 is required for enterotoxicity seen in animal models. Effector proteins secreted from T3SS2 have been previously shown to promote colonization of the intestinal epithelium, invasion of host cells, and destruction of the epithelial monolayer. In this study, we identify VPA1380, a T3SS2 effector protein that is toxic when expressed in yeast. Bioinformatic analyses revealed that VPA1380 is highly similar to the inositol hexakisphosphate (IP6)-inducible cysteine protease domains of several large bacterial toxins. Mutations in conserved catalytic residues and residues in the putative IP6-binding pocket abolished toxicity in yeast. Furthermore, VPA1380 was not toxic in IP6 deficient yeast cells. Therefore, our findings suggest that VPA1380 is a cysteine protease that requires IP6 as an activator.
    PLoS ONE 08/2014; 9(8)(8):e104387. DOI:10.1371/journal.pone.0104387 · 3.23 Impact Factor
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