Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

Awasthi, Sharda Prasad; Asakura, Masahiro; Chowdhury, Nityananda; Neogi, Sucharit Basu; Hinenoya, Atsushi; Golbar, Hossain M.; Yamate, Jyoji; Arakawa, Eiji; Tada, Toshiji; Ramamurthy, Thandavarayan; Yamasaki, Shinji

doi:10.1128/iai.00982-12

Cited by 53 publications

(96 citation statements)

References 52 publications

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“…However, these strains harbored other virulence genes similar to non-O1/non-O139. Both chxA and TTSS genes were frequently found among non-O1/non-O139 pathogenic strains and associated with diarrhea [36, 51, 55]. However, the environmental O1 strains in this study harbored chxA gene (TC22) and TTSS (MK14), indicating virulence potential to cause disease.…”

Section: Discussionmentioning

confidence: 68%

Characterization and Genetic Variation of Vibrio cholerae Isolated from Clinical and Environmental Sources in Thailand

et al. 2017

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Cholera is still an important public health problem in several countries, including Thailand. In this study, a collection of clinical and environmental V. cholerae serogroup O1, O139, and non-O1/non-O139 strains originating from Thailand (1983 to 2013) was characterized to determine phenotypic and genotypic traits and to investigate the genetic relatedness. Using a combination of conventional methods and whole genome sequencing (WGS), 78 V. cholerae strains were identified. WGS was used to determine the serogroup, biotype, virulence, mobile genetic elements, and antimicrobial resistance genes using online bioinformatics tools. In addition, phenotypic antimicrobial resistance was determined by the minimal inhibitory concentration (MIC) test. The 78 V. cholerae strains belonged to the following serogroups O1: (n = 44), O139 (n = 16) and non-O1/non-O139 (n = 18). Interestingly, we found that the typical El Tor O1 strains were the major cause of clinical cholera during 1983–2000 with two Classical O1 strains detected in 2000. In 2004–2010, the El Tor variant strains revealed genotypes of the Classical biotype possessing either only ctxB or both ctxB and rstR while they harbored tcpA of the El Tor biotype. Thirty O1 and eleven O139 clinical strains carried CTXϕ (Cholera toxin) and tcpA as well four different pathogenic islands (PAIs). Beside non-O1/non-O139, the O1 environmental strains also presented chxA and Type Three Secretion System (TTSS). The in silico MultiLocus Sequence Typing (MLST) discriminated the O1 and O139 clinical strains from other serogroups and environmental strains. ST69 was dominant in the clinical strains belonging to the 7th pandemic clone. Non-O1/non-O139 and environmental strains showed various novel STs indicating genetic variation. Multidrug-resistant (MDR) strains were observed and conferred resistance to ampicillin, azithromycin, nalidixic acid, sulfamethoxazole, tetracycline, and trimethoprim and harboured variants of the SXT elements.For the first time since 1986, the presence of V. cholerae O1 Classical was reported causing cholera outbreaks in Thailand. In addition, we found that V. cholerae O1 El Tor variant and O139 were pre-dominating the pathogenic strains in Thailand. Using WGS and bioinformatic tools to analyze both historical and contemporary V. cholerae circulating in Thailand provided a more detailed understanding of the V. cholerae epidemiology, which ultimately could be applied for control measures and management of cholera in Thailand.

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Section: Discussionmentioning

confidence: 68%

Characterization and Genetic Variation of Vibrio cholerae Isolated from Clinical and Environmental Sources in Thailand

et al. 2017

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“…Given that the environment is dominated by non-O1/non-O139 strains, this observation suggests that these virulence factors probably do not promote fitness in the aquatic niche although there is some data that challenges this conclusion for at least chitin binding lectins (Kirn et al 2005). Various typing methods and deep sequencing has enabled more sensitive surveillance of CTX–ϕ in strains isolated from the environment (Rivera et al 2001; Singh et al 2001; Pang et al 2007; Awasthi et al 2012; Hasan et al 2012; Sealfon et al 2012; Sellek et al 2012). The prevalent assumption that the presence of toxigenic strains in water provides proof that toxigenic strain occupy a stable environmental niche needs to be readdressed with modern methods that might differentiate between contamination of the environment by nearby cholera victims as opposed to these strains maintaining themselves within the environment in the absence of infected humans.…”

Section: Conventional Genomics and Established Virulence Islandsmentioning

confidence: 99%

Genomic Science in Understanding Cholera Outbreaks and Evolution of Vibrio cholerae as a Human Pathogen

Robins

Mekalanos

2014

Cholera Outbreaks

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Modern genomic and bioinformatic approaches have been applied to interrogate the V. cholerae genome, the role of genomic elements in cholera disease, and the origin, relatedness, and dissemination of epidemic strains. A universal attribute of choleragenic strains includes a repertoire of pathogenicity islands and virulence genes, namely the CTX–ϕ prophage and Toxin Co-regulated Pilus (TCP) in addition to other virulent genetic elements including those referred to as Seventh Pandemic Islands. During the last decade, the advent of Next Generation Sequencing (NGS) has provided highly resolved and often complete genomic sequences of epidemic isolates in addition to both clinical and environmental strains isolated from geographically unconnected regions. Genomic comparisons of these strains, as was completed during and following the Haitian outbreak in 2010, reveals that most epidemic strains appear closely related, regardless of region of origin. Non-O1 clinical or environmental strains may also possess some virulence islands, but phylogenic analysis of the core genome suggests they are more diverse and distantly related than those isolated during epidemics. Like Haiti, genomic studies that examine both the Vibrio core- and pan-genome in addition to Single Nucleotide Polymorphisms (SNPs) conclude that a number of epidemics are caused by strains that closely resemble those in Asia, and often appear to originate there and then spread globally. The accumulation of SNPs in the epidemic strains over time can then be applied to better understand the evolution of the V. cholerae genome as an etiological agent.

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“…While most of these putative virulence factors are expressed in only a fraction of clinical NOVC isolates, RTX, HapA and VCC are expressed in almost all V. cholerae serogroups and are therefore more promising as potential toxigenic factors [2], [9], [11]. VCC is a particularly interesting candidate; in a study using a streptomycin-fed murine model of disease, VCC was shown to be the predominant cause of death [12].…”

Section: Introductionmentioning

confidence: 99%

Outer Membrane Vesicles Mediate Transport of Biologically Active Vibrio cholerae Cytolysin (VCC) from V. cholerae Strains

et al. 2014

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BackgroundOuter membrane vesicles (OMVs) released from Gram-negative bacteria can serve as vehicles for the translocation of virulence factors. Vibrio cholerae produce OMVs but their putative role in translocation of effectors involved in pathogenesis has not been well elucidated. The V. cholerae cytolysin (VCC), is a pore-forming toxin that lyses target eukaryotic cells by forming transmembrane oligomeric β-barrel channels. It is considered a potent toxin that contributes to V. cholerae pathogenesis. The mechanisms involved in the secretion and delivery of the VCC have not been extensively studied.Methodology/Principal FindingsOMVs from V. cholerae strains were isolated and purified using a differential centrifugation procedure and Optiprep centrifugation. The ultrastructure and the contents of OMVs were examined under the electron microscope and by immunoblot analyses respectively. We demonstrated that VCC from V. cholerae strain V:5/04 was secreted in association with OMVs and the release of VCC via OMVs is a common feature among V. cholerae strains. The biological activity of OMV-associated VCC was investigated using contact hemolytic assay and epithelial cell cytotoxicity test. It showed toxic activity on both red blood cells and epithelial cells. Our results indicate that the OMVs architecture might play a role in stability of VCC and thereby can enhance its biological activities in comparison with the free secreted VCC. Furthermore, we tested the role of OMV-associated VCC in host cell autophagy signalling using confocal microscopy and immunoblot analysis. We observed that OMV-associated VCC triggered an autophagy response in the target cell and our findings demonstrated for the first time that autophagy may operate as a cellular defence mechanism against an OMV-associated bacterial virulence factor.Conclusion/SignificanceBiological assays of OMVs from the V. cholerae strain V:5/04 demonstrated that OMV-associated VCC is indeed biologically active and induces toxicity on mammalian cells and furthermore can induce autophagy.

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Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

Cited by 53 publications

References 52 publications

Characterization and Genetic Variation of Vibrio cholerae Isolated from Clinical and Environmental Sources in Thailand

Characterization and Genetic Variation of Vibrio cholerae Isolated from Clinical and Environmental Sources in Thailand

Genomic Science in Understanding Cholera Outbreaks and Evolution of Vibrio cholerae as a Human Pathogen

Outer Membrane Vesicles Mediate Transport of Biologically Active Vibrio cholerae Cytolysin (VCC) from V. cholerae Strains

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