Dataset Information

CitAB Two-Component System-Regulated Citrate Utilization Contributes to Vibrio cholerae Competitiveness with the Gut Microbiota.

ABSTRACT: Citrate is a ubiquitous compound and can be utilized by many bacterial species, including enteric pathogens, as a carbon and energy source. Genes involved in citrate utilization have been extensively studied in some enteric bacteria, such as Klebsiella pneumoniae; however, their role in pathogenesis is still not clear. In this study, we investigated citrate utilization and regulation in Vibrio cholerae, the causative agent of cholera. The putative anaerobic citrate fermentation genes in V. cholerae, consisting of citCDEFXG, citS-oadGAB, and the two-component system (TCS) genes citAB, are highly homologous to those in K. pneumoniae Deletion analysis shows that these cit genes are essential for V. cholerae growth when citrate is the sole carbon source. The expression of citC and citS operons was dependent on citrate and CitAB, whose transcription was autorepressed and regulated by another TCS regulator, ArcA. In addition, citrate fermentation was under the control of catabolite repression. Mouse colonization experiments showed that V. cholerae can utilize citrate in vivo using the citrate fermentation pathway and that V. cholerae likely needs to compete with other members of the gut microbiota to access citrate in the gut.

SUBMITTER: Liu M

PROVIDER: S-EPMC6386541 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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CitAB Two-Component System-Regulated Citrate Utilization Contributes to Vibrio cholerae Competitiveness with the Gut Microbiota.

Liu Ming M Hao Guijuan G Li Zhe Z Zhou Yitian Y Garcia-Sillas Reyna R Li Jie J Wang Hui H Kan Biao B Zhu Jun J

Infection and immunity 20190221 3

Citrate is a ubiquitous compound and can be utilized by many bacterial species, including enteric pathogens, as a carbon and energy source. Genes involved in citrate utilization have been extensively studied in some enteric bacteria, such as Klebsiella pneumoniae; however, their role in pathogenesis is still not clear. In this study, we investigated citrate utilization and regulation in Vibrio cholerae, the causative agent of cholera. The putative anaerobic citrate fermentation gen ...[more]

PMID: 30559220

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Project description:Given the global burden of diarrhoeal diseases, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhoea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. Here we conduct a detailed time-series metagenomic study of faecal microbiota collected during the acute diarrhoeal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children. To define the underlying mechanisms, we introduce into gnotobiotic mice an artificial community composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children. One of the species, Ruminococcus obeum, exhibits consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obeum luxS (autoinducer-2 (AI-2) synthase) expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing-mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants discloses that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.

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Dataset Information

CitAB Two-Component System-Regulated Citrate Utilization Contributes to Vibrio cholerae Competitiveness with the Gut Microbiota.

Publications

CitAB Two-Component System-Regulated Citrate Utilization Contributes to <i>Vibrio cholerae</i> Competitiveness with the Gut Microbiota.

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