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Total Synthesis of the Complete Protective Antigen of Vibrio cholerae O139.

ABSTRACT: The first chemical synthesis of the complete protective O-antigen of a human-disease-causing pathogenic bacterium is described. The synthesis involved a protecting-group strategy that facilitated the regioselectivity of the key transformations, stereoselective glycosylation reactions, and enabled the one-step global deprotection of the completely assembled, fully protected, phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final amino-group-functionalized, linker-equipped antigen was obtained in a form ready for conjugation to suitable carriers, for example, proteins, to yield immunogens.

SUBMITTER: Soliman SE

PROVIDER: S-EPMC5165651 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Total Synthesis of the Complete Protective Antigen of Vibrio cholerae O139.

Soliman Sameh E SE Kováč Pavol P

Angewandte Chemie (International ed. in English) 20160914 41

The first chemical synthesis of the complete protective O-antigen of a human-disease-causing pathogenic bacterium is described. The synthesis involved a protecting-group strategy that facilitated the regioselectivity of the key transformations, stereoselective glycosylation reactions, and enabled the one-step global deprotection of the completely assembled, fully protected, phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final amino-group-functionalized, linker-equipped antige ...[more]

PMID: 27623688

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New Variant of Vibrio cholerae O139 in Odisha, India.

Project description: Not available

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Antimicrobial Susceptibility of Environmental Non-O1/Non-O139 Vibrio cholerae Isolates.

Project description:Vibrio cholerae serogroups O1 and O139 are the causative agents of cholera disease. There are more than 200 serogroups in this species that are termed V. cholerae non-O1/non-O139. Non-O1/non-O139 strains can cause gastroenteritis and cholera like diarrhea, wound infections, external otitis, and bacteraemia that may lead to mortality. Previous antimicrobial susceptibility studies were conducted mainly on O1/O139 serogroups and on clinical isolates. Our aim was to study and compare the antimicrobial susceptibilities of non-O1/non-O139 environmental strains isolated from chironomids, fish, and waterfowl. Significant differences were found in the antimicrobial susceptibilities between the environmental strains that were isolated from three different reservoir habitats. Significant increase in minimum inhibitory concentrations (MICs) of ampicillin and chloramphenicol was found in chironomid isolates from 2009 compared to those from 2005. V. cholerae isolates from different waterfowl species displayed the highest MIC values to chloramphenicol and trimethoprim-sulfamethoxazole (SXT), while chironomid isolates demonstrated the highest MIC values toward ampicillin. Isolates from fish and waterfowl showed high MIC values toward doxycycline. No significant differences were found between the MICs of isolates from the different waterfowl species. The percentage of antimicrobial resistance among V. cholerae isolates from waterfowl was the highest compared to the abundance of antimicrobial resistant isolates from chironomids or fish. The antimicrobial resistance genes can be carried on mobile genetic elements, thus, waterfowl may act as reservoirs for these elements and may spread them all over the globe. Data regarding treatment with antimicrobial agents toward V. cholerae non-O1/non-O139 serogroups is lacking and therefore further studies are needed.

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Genomic Epidemiology of Vibrio cholerae O139, Zhejiang Province, China, 1994-2018.

Project description:Cholera caused by Vibrio cholerae O139 was first reported in Bangladesh and India in 1992. To determine the genomic epidemiology and origins of O139 in China, we sequenced 104 O139 isolates collected from Zhejiang Province, China, during 1994-2018 and compared them with 57 O139 genomes from other countries in Asia. Most Zhejiang isolates fell into 3 clusters (C1-C3), which probably originated in India (C1) and Thailand (C2 and C3) during the early 1990s. Different clusters harbored different antimicrobial resistance genes and IncA/C plasmids. The integrative and conjugative elements carried by Zhejiang isolates were of a new type, differing from ICEVchInd4 and SXTMO10 by single-nucleotide polymorphisms and presence of genes. Quinolone resistance-conferring mutations S85L in parC and S83I in gyrA occurred in 71.2% of the Zhejiang isolates. The ctxB copy number differed among the 3 clusters. Our findings provided new insights for prevention and control of O139 cholera .

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Comparison of Vibrio cholerae O139 with V. cholerae O1 classical and El Tor biotypes.

Project description:Vibrio cholerae O139 is a recently identified non-O1 V. cholerae strain responsible for outbreaks of epidemic cholera in India, Bangladesh, and Thailand in the past 2 years. Other workers have demonstrated the presence of the cholera toxin genetic element in V. cholerae O139, unlike the situation for other non-O1 V. cholerae strains. We sought to compare further this strain with strains of V. cholerae O1, classical and El Tor biotypes, by classic microbiologic methods, Southern blot analysis for restriction fragment length polymorphisms with probes for iron-regulated genes of V. cholerae O1, and comparisons of outer membrane protein profiles. Our results were similar for V. cholerae O139 and the El Tor biotype of V. cholerae O1, with the exception of the constitutive expression in V. cholerae O139 of OmpS, an outer membrane protein that was maltose inducible in comparison strains of V. cholerae O1.

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Differential expression CTX positive and CTX negative Vibrio cholerae O139 strains

Project description:To gain an insight into the changes between CTX-positive and -negative strain, apart from the CTX phage deletion, we carried out microarray analysis and whole genome sequencing of both strains

2017-10-12 | GSE104843 | GEO

Prevailing clone (ST69) of Vibrio cholerae O139 in India over 10 years.

Project description:Vibrio cholerae is responsible for the cause of severe life-threatening infection known as cholera. The study aimed to analyze the genetic make-up of V. cholerae O139 isolates from India and compare its phylogeny with the global strains. The genome data revealed that all isolates were of same sequence type (ST69) which belongs to seventh pandemic clone, with same virulence gene profile and, antimicrobial resistance gene profile except for two isolates. No known CRISPR repeats were identified in any of these isolates. Three different phages were identified among the isolates. All the isolates were found to harbour intSXT and seventh pandemic-specific gene (VC2346). Results from this study enhance our understanding on the persistence of ST69 V. cholerae O139 over 20 years.

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Characterization of Vibrio cholerae O139 of an Aquatic Isolate in Northern Vietnam.

Project description:During the cholera survey in Namdinh province (northern Vietnam) in July, 2010, one strain of Vibrio cholerae O139 was isolated from 7 environmental water samples positive for ctxA, toxR,VCO139 genes and named as V. cholerae O139, ND1 strain. This strain was lysogenic harbouring a genome similar to the filamentous phage fs1. The replicative form DNA of this phage (named as ND1-fs1, 6856 bp) was sequenced and compared with the other filamentous phages. The filamentous phage ND1-fs1 integrates into the region between ctxB and rtxA genes. The genetic organization of the CTXϕ of V. cholerae O139, strain ND1 was determined and the schematic representation of the genetic organization was shown together with the ND1-fs1 prophage.

| S-EPMC3282888 | biostudies-literature

Genetic rearrangements in the rfb regions of Vibrio cholerae O1 and O139.

Project description:The recent emergence of a pathogenic new non-O1 serotype (O139) of Vibrio cholerae has led to numerous studies in an attempt to identify the origins of this new strain. Our studies indicate that O139 strains have clear differences in the surface polysaccharides when compared with O1 strains: the lipopolysaccharide can be described as semi-rough. Southern hybridization with the O1 rfb region demonstrates that O139 strains no longer contain any of the rfb genes required for the synthesis of the O1 O-antigen or its modification and also lack at least 6 kb of additional contiguous DNA. However, O139 strains have retained rfaD and have a single open reading frame closely related to three small open reading frames of the O1 rfb region. This region is closely related to the H-repeat of Escherichia coli and to the transposases of a number of insertion sequence elements and has all the features of an insertion sequence element that has been designated VcIS1. Transposon insertion mutants defective in O139 O-antigen (and capsule) biosynthesis map to the same fragment as VcIS1. Preliminary sequence data of complementing clones indicate that this DNA encodes a galactosyl-transferase and other enzymes for the utilization of galactose in polysaccharide biosynthesis. We propose a mechanism by which both the Ogawa serotype of O1 strains and the O139 serotype strains may have evolved.

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Survey on antimicrobial resistance patterns in Vibrio vulnificus and Vibrio cholerae non-O1/non-O139 in Germany reveals carbapenemase-producing Vibrio cholerae in coastal waters.

Project description:An increase in the occurrence of potentially pathogenic Vibrio species is expected for waters in Northern Europe as a consequence of global warming. In this context, a higher incidence of Vibrio infections is predicted for the future and forecasts suggest that people visiting and living at the Baltic Sea are at particular risk. This study aimed to investigate antimicrobial resistance patterns among Vibrio vulnificus and Vibrio cholerae non-O1/non-O139 isolates that could pose a public health risk. Antimicrobial susceptibility of 141 V. vulnificus and 184 V. cholerae non-O1/non-O139 strains isolated from German coastal waters (Baltic Sea and North Sea) as well as from patients and retail seafood was assessed by broth microdilution and disk diffusion. Both species were susceptible to most of the agents tested (12 subclasses) and no multidrug-resistance was observed. Among V. vulnificus isolates, non-susceptibility was exclusively found toward aminoglycosides. In case of V. cholerae, a noticeable proportion of strains was non-susceptible to aminopenicillins and aminoglycosides. In addition, resistance toward carbapenems, quinolones, and folate pathway inhibitors was sporadically observed. Biochemical testing indicated the production of carbapenemases with unusual substrate specificity in four environmental V. cholerae strains. Most antimicrobial agents recommended for treatment of V. vulnificus and V. cholerae non-O1/non-O139 infections were found to be effective in vitro. However, the occurrence of putative carbapenemase producing V. cholerae in German coastal waters is of concern and highlights the need for systematic monitoring of antimicrobial susceptibility in potentially pathogenic Vibrio spp. in Europe.

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Draft Genome Sequence of Non-O1 and Non-O139 Vibrio cholerae Strain VCC19.

Project description:Vibrio cholerae O1 is the causative agent of cholera and is ubiquitous in the aquatic environment, while V. cholerae strains non-O1 and non-O139 are recognized as causative agents of sporadic and localized outbreaks of diarrhea. Here, we report the complete sequence of a non-O1 and non-O139 V. cholerae strain (VCC19), which was isolated from the environment in Brazil. The sequence includes the integrative conjugative element (ICE). This paper is the first report of the presence of such an element in a V. cholerae strain isolated in Brazil.

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