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: 9.67). 11/2007; 104(43):17117-22. DOI: 10.1073/pnas.0703196104
Source: PubMed


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.

Download full-text


Available from: Dara L Burdette
  • Source
    • "Microbial pathogens modulate the host cell actin cytoskeleton to control phagocytosis, adhesion, cell–cell contacts, movement within the cytosol, spreading to neighboring cells, or development of a niche viable for intracellular bacterial replication (Kumar and Valdivia 2008; Carabeo 2011; Haglund and Welch 2011). This is accomplished by effector proteins that hijack the major eukaryotic actin nucleators Arp2/3 complex and formins (Truong et al. 2014), modulate key regulators of actin dynamics (e.g., Rho GTPases) (Hardt et al. 1998; Egile et al. 1999; Stender et al. 2000; Zhou et al. 2001; Patel and Galan 2006; Rottner et al. 2010), or directly polymerize actin (Hayward and Koronakis 1999; Jewett et al. 2006; Liverman et al. 2007; Haglund et al. 2010; Franco et al. 2012). The actin network also plays a fundamental role in the Legionella infection process. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The Legionella pneumophila effector protein VipA is an actin nucleator that co-localizes with actin filaments and early endosomes in infected macrophages and which interferes with organelle trafficking when expressed in yeast. To identify the regions of VipA involved in its subcellular localization and functions, we ectopically expressed specific VipA mutant proteins in eukaryotic cells. This indicated that the characteristic punctate distribution of VipA depends on its NH2 -terminal (amino acid residues 1-133) and central coiled-coil (amino acid residues 133-206) regions, and suggested a role for the COOH-terminal (amino acid residues 206-339) region in association with actin filaments and for the NH2 -terminal in co-localization with early endosomes. Co-immunoprecipitation and in vitro assays showed that the COOH-terminal region of VipA is necessary and sufficient to mediate actin binding, and is essential but insufficient to induce microfilament formation. Assays in yeast revealed that the NH2 and the COOH-terminal regions, and possibly an NPY motif within the NH2 region of VipA, are necessary for interference with organelle trafficking. Overall, this suggests that subversion of eukaryotic vesicular trafficking by VipA involves both its ability to associate with early endosomes via its NH2 -terminal region and its capacity to bind and polymerize actin through its COOH-terminal region.
    Full-text · Article · Dec 2015 · MicrobiologyOpen
  • Source
    • "(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. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Mar 2015 · Frontiers in Microbiology
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Dec 2014 · Cellular Microbiology
Show more