Hemolysin and the Multifunctional Autoprocessing RTX Toxin Are Virulence Factors during Intestinal Infection of Mice with
            <i>Vibrio cholerae</i>
            El Tor O1 Strains

Olivier, Verena; Haines, G. Kenneth; Tan, Yinling; Satchell, K.J.F.

doi:10.1128/iai.00506-07

Cited by 89 publications

(105 citation statements)

References 45 publications

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“…Although we could not predict the cell elongation factor of Vc450 from the proteome, we hypothesize that the RTX toxin is the most likely candidate as the cytotoxic substance, as it is a pore-forming toxin and the CHO cells were not completely lysed during the assay. In V. cholerae, RTX toxin acts as a virulence cofactor disrupting the cell wall integrity of the host cells (Olivier et al, 2007), whereas the V. vulnificus RTX toxin causes cell lysis through pore formation, resulting in the degradation of phagocytic host cells (Lo et al, 2011). An increased expression of RTX toxin in Vc450 at the virulent temperature of 27 1C may allow for increased survival of Vc450 owing to degradation of the host's innate immune system.…”

Section: Resultsmentioning

confidence: 99%

Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus

Kimes

Grim

Johnson³

et al. 2011

The ISME Journal

230

200

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Sea surface temperatures (SST) are rising because of global climate change. As a result, pathogenic Vibrio species that infect humans and marine organisms during warmer summer months are of growing concern. Coral reefs, in particular, are already experiencing unprecedented degradation worldwide due in part to infectious disease outbreaks and bleaching episodes that are exacerbated by increasing SST. For example, Vibrio coralliilyticus, a globally distributed bacterium associated with multiple coral diseases, infects corals at temperatures above 27 1C. The mechanisms underlying this temperature-dependent pathogenicity, however, are unknown. In this study, we identify potential virulence mechanisms using whole genome sequencing of V. coralliilyticus ATCC (American Type Culture Collection) BAA-450. Furthermore, we demonstrate direct temperature regulation of numerous virulence factors using proteomic analysis and bioassays. Virulence factors involved in motility, host degradation, secretion, antimicrobial resistance and transcriptional regulation are upregulated at the higher virulent temperature of 27 1C, concurrent with phenotypic changes in motility, antibiotic resistance, hemolysis, cytotoxicity and bioluminescence. These results provide evidence that temperature regulates multiple virulence mechanisms in V. coralliilyticus, independent of abundance. The ecological and biological significance of this temperature-dependent virulence response is reinforced by climate change models that predict tropical SST to consistently exceed 27 1C during the spring, summer and fall seasons. We propose V. coralliilyticus as a model Gram-negative bacterium to study temperature-dependent pathogenicity in Vibrio-related diseases.

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Section: Resultsmentioning

confidence: 99%

Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus

Kimes

Grim

Johnson³

et al. 2011

The ISME Journal

230

200

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“…In addition to CT, strains of the El Tor biotype secrete accessory toxins, including the pore-forming toxin hemolysin, the actin cross-linking multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, and the secreted metalloprotease hemagglutinin (HA)/protease (6,7). These factors have been linked to evasion of neutrophil clearance during infection, facilitating colonization of the small intestine (8)(9)(10).…”

mentioning

confidence: 99%

Mechanisms of Inflammasome Activation by Vibrio cholerae Secreted Toxins Vary with Strain Biotype

et al. 2015

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Activation of inflammasomes is an important aspect of innate immune responses to bacterial infection. Recent studies have linked Vibrio cholerae secreted toxins to inflammasome activation by using murine macrophages. To increase relevance to human infection, studies of inflammasome-dependent cytokine secretion were conducted with the human THP-1 monocytic cell line and corroborated in primary human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical strains of V. cholerae activated ASC (apoptosis-associated speck-like protein-containing a CARD domain)-dependent release of interleukin-1␤ (IL-1␤) when cultured with human THP-1 cells, but the pattern of induction was distinct, depending on the repertoire of toxins the strains produced. El Tor biotype strains induced release of IL-1␤ dependent on NOD-like receptor family pyrin domain-containing 3 (NLRP3) and ASC due to the secreted pore-forming toxin hemolysin. Unlike in studies with mouse macrophages, the MARTX toxin did not contribute to IL-1␤ release from human monocytic cells. Classical biotype strains, which do not produce either hemolysin or the MARTX toxin, activated low-level IL-1␤ release that was induced by cholera toxin (CT) and dependent on ASC but independent of NLRP3 and pyroptosis. El Tor strains likewise showed increased IL-1␤ production dependent on CT when the hemolysin gene was deleted. In contrast to studies with murine macrophages, this phenotype was dependent on a catalytically active CT A subunit capable of inducing production of cyclic AMP and not on the B subunit. These studies demonstrate that the induction of the inflammasome in human THP-1 monocytes and in PBMCs by V. cholerae varies with the biotype and is mediated by both NLRP3-dependent and -independent pathways. V ibrio cholerae is the causative agent of the diarrheal disease cholera. The O1 serogroup, which is most associated with disease, is divided into two biotypes, classical and El Tor. Classical strains were responsible for the six cholera pandemics that occurred during the 19th century and the first half of the 20th century and are noted for their severe clinical presentation. In 1961, the El Tor strains emerged as the cause of the ongoing seventh pandemic, completely displacing the classical strains from the environment and as a cause of cholera in humans (1). These strains colonize the intestine more effectively and spread between hosts more efficiently but cause fewer deaths and significantly more asymptomatic colonization (2).The primary virulence factor for pandemic cholera strains is cholera toxin (CT), an ADP-ribosylating toxin that disables the G␣ s subunit, resulting in increased cyclic AMP (cAMP) production and secretion of fluid from enterocytes due to the opening of chloride channels. The toxin is composed of the catalytically active A (CTA) subunit associated with five CTB subunits that bind to surface GM 1 gangliosides, facilitating toxin endocytosis (3). In addition to enterotoxigenic activity, CT has also been demonstrated to have immunomodulat...

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“…Some V. cholerae virulence factors are well characterized, such as cholera toxin and toxin coregulated pilus (1). The contributions of other virulence factors to V. cholerae pathogenesis are beginning to be elucidated (2,3), and one putative accessory virulence factor is the type VI secretion system (T6SS).…”

mentioning

confidence: 99%

In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system is associated with intestinal inflammation

Mekalanos

2010

Proc. Natl. Acad. Sci. U.S.A.

192

168

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Type VI secretion systems (T6SSs) have recently been recognized as potential virulence determinants of many Gram-negative bacterial pathogens. Although mechanistic studies are lacking, T6SS-dependent phenotypes can be observed in various animal models of infection. Presumably translocation of T6SS effectors into target cells is involved in virulence, but few such effectors have been identified. A hallmark of T6SS function is the in vitro secretion of Hcp and VgrG proteins, which are thought to form part of an extracellular secretion apparatus. One well-characterized effector domain is the C-terminal actin cross-linking domain (ACD) of the VgrG-1 protein, constitutively secreted by the T6SS of Vibrio cholerae strain V52. Previous work indicated that translocation of VgrG-1 occurred only after endocytic uptake of bacteria into host cells. VgrG-1-induced actin cross-linking impaired phagocytic activity of host cells, eventually causing cell death. To determine whether V. cholerae T6SS is functional during animal infection, derivatives of V52 were used to infect infant mice. In this infection model a diarrheal response occurred, and actin cross-linking could be detected. These host responses were dependent on a functional T6SS and on the ACD of VgrG-1. Gene expression and histologic studies showed innate immune activation and immune cell infiltration in the intestinal lumen. The T6SS-dependent inflammatory response was also associated with increased recovery of V. cholerae from the intestine. We conclude that the T6SS of V52 induces an inflammatory diarrhea that facilitates replication of V. cholerae within the intestine.innate immunity | VgrG | virulence effector | ACD | MARTX

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Hemolysin and the Multifunctional Autoprocessing RTX Toxin Are Virulence Factors during Intestinal Infection of Mice with Vibrio cholerae El Tor O1 Strains

Cited by 89 publications

References 45 publications

Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus

Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus

Mechanisms of Inflammasome Activation by Vibrio cholerae Secreted Toxins Vary with Strain Biotype

In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system is associated with intestinal inflammation

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