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.

Transcriptional profiling of Salmonella enterica serovar Enteritidis exposed to ethanolic extract of organic cranberry pomace

“…Citrate can be utilized by Salmonella as a carbon and energy source using several catabolic fermentative pathways involving genes located in two divergently transcribed operons, citCDEFG and citS-oadGAB-citAB , whose expression is modulated by the citrate-sensing CitA/CitB two-component system [51]. CitAB has been shown to contribute to Vibrio cholerae competitiveness within the gut microbiota; however, the role of citrate fermentation in pathogenic bacteria during infection is not clear [52]. Since, cranberry extract is a source of citrate, it may serve as a carbon source during the TCA cycle, to play an important regulatory molecule in the control of glycolysis and lipid metabolism [37].…”

The Interface of Vibrio cholerae and the Gut Microbiome

“…Supplementation of citrate in an adult mouse colonization model led to a loss of fitness of a citrate fermentation mutant (ΔcitAB) compared to wild-type in the presence of gut microbes, and promoted microbial growth in general in the small intestine. 154 The role of general nutrient availability is also highlighted by several studies focusing on the role of cyclic AMP (cAMP) receptor protein (CRP) on the regulation of various virulence-associated pathways in V. cholerae. In the absence of preferred nutrient sources, possibly via inter-microbial competition in vivo, CRP-cAMP is able to activate components of the T6SS.…”

Ohr and OhrR Are Critical for Organic Peroxide Resistance and Symbiosis in Azorhizobium caulinodans ORS571

“…The binding of OhrR protein or its mutated derivatives to target promoters was performed, as described previously [59,60]. The promoter region of ohr was amplified and purified as DNA probe (181 bp).…”