Effect of Bile on the Cell Surface Permeability Barrier and Efflux System of
            <i>Vibrio cholerae</i>

Chatterjee, Arpita; Chaudhuri, Sutapa; Saha, Goutam; Gupta, S; Chowdhury, Rukhsana

doi:10.1128/jb.186.20.6809-6814.2004

Cited by 52 publications

(43 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Campylobacter, inactivation of the cmeB gene resulted in a drastic increase in bile sensitivity and the cmeB null mutant was unable to colonize the intestinal tracts of chickens (22). In E. coli, Salmonella, and Vibrio cholerae, the AcrAB-TolC efflux pump (a homolog of the CmeABC pump) contributes to bile resistance and is inducible by bile salts (4,37,42). Given that bile acids are a natural component in the intestinal environment, the accumulating evidence on efflux-mediated bile resistance strongly suggests that efflux of bile acids is the natural function of some RND-type transporters (e.g., AcrAB-TolC and CmeABC) in enteric bacteria.…”

Section: Discussionmentioning

confidence: 99%

Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump inCampylobacter jejuni

Cagliero²,

et al. 2005

View full text Add to dashboard Cite

CmeABC, a multidrug efflux pump, is involved in the resistance of Campylobacter jejuni to a broad spectrum of antimicrobial agents and is essential for Campylobacter colonization in animal intestine by mediating bile resistance. Previously, we have shown that expression of this efflux pump is under the control of a transcriptional repressor named CmeR. Inactivation of CmeR or mutation in the cmeABC promoter (P cmeABC ) region derepresses cmeABC, leading to overexpression of this efflux pump. However, it is unknown if the expression of cmeABC can be conditionally induced by the substrates it extrudes. In this study, we examined the expression of cmeABC in the presence of various antimicrobial compounds. Although the majority of the antimicrobials tested did not affect the expression of cmeABC, bile salts drastically elevated the expression of this efflux operon. The induction was observed with both conjugated and unconjugated bile salts and was in a dose-and time-dependent manner. Experiments using surface plasmon resonance demonstrated that bile salts inhibited the binding of CmeR to P cmeABC , suggesting that bile compounds are inducing ligands of CmeR. The interaction between bile salts and CmeR likely triggers conformational changes in CmeR, resulting in reduced binding affinity of CmeR to P cmeABC . Bile did not affect the transcription of cmeR, indicating that altered expression of cmeR is not a factor in bile-induced overexpression of cmeABC. In addition to the CmeR-dependent induction, some bile salts (e.g., taurocholate) also activated the expression of cmeABC by a CmeR-independent pathway. Consistent with the elevated production of CmeABC, the presence of bile salts in culture media resulted in increased resistance of Campylobacter to multiple antimicrobials. These findings reveal a new mechanism that modulates the expression of cmeABC and further support the notion that bile resistance is a natural function of CmeABC.

show abstract

Section: Discussionmentioning

confidence: 99%

Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump inCampylobacter jejuni

Cagliero²,

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Bile modulates CT expression, outer membrane protein expression, motility, and induction of efflux systems (44). Its pleiotropic effects are complex given that it is a heterogenous mixture of electrolytes, bile acids, phospholipids, cholesterol, and bilirubin.…”

Section: Discussionmentioning

confidence: 99%

Bile acids induce cholera toxin expression in Vibrio cholerae in a ToxT-independent manner

Hung

Mekalanos²

2005

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

149

128

View full text Add to dashboard Cite

The production of cholera toxin (CT) during Vibrio cholerae infection results in the hallmark diarrhea that characterizes the disease cholera. The transmembrane protein ToxR was originally identified as a functional transcriptional activator of ctxAB in a heterologous Escherichia coli system. However, direct ToxR activation of the ctxAB promoter in V. cholerae has not been previously demonstrated. Instead, a regulatory cascade has been defined in which the activators ToxRS and TcpPH modulate ctxAB expression by acting in concert to transcriptionally activate another regulator, ToxT. ToxT, in turn, directly activates ctxAB expression as well as expression of the tcp genes and other virulence-associated genes. In this study, we show that ToxRS directly activates ctxAB in a ToxT-independent manner in a classical biotype V. cholerae, and that this activation requires the presence of bile acids. Although the levels of CT induced by this mechanism are lower than levels induced under other in vitro conditions, the bile-dependent conditions described here are more physiologic, being independent of pH and temperature. We further show that the inability of bile acids to stimulate ToxRS-dependent expression of CT in El Tor biotype strains is related to the differences between classical and El Tor ctxAB promoters, which differ in the number of heptad TTTTGAT repeats in their respective upstream regions. The ability of bile acids to stimulate direct activation of ctxAB by ToxRS depends upon the transmembrane domain of ToxR, which may interact with bile acids in the inner membrane of V. cholerae. The Gram-negative bacterium Vibrio cholerae is the infectious agent that causes the severe human diarrheal disease cholera (1). Two major virulence factors, cholera toxin (CT) and the toxin-coregulated pilus (TCP), play major roles in the pathogenesis of this infection. Secretion of CT, an ADP-ribosylating toxin encoded in the genome of the filamentous, lysogenic CTX⌽ phage, results in elevated cAMP levels in intestinal epithelial cells and subsequent secretory diarrhea (2). The regulation of CT and TCP expression has been studied intensely and has been reported to respond to temperature, pH, osmolarity, bile salts, and certain amino acids in vitro (3, 4); nevertheless, a clear understanding of the in vivo environmental stimuli that trigger CT and TCP production remains elusive.The first transcriptional regulator of CT production identified was ToxR, a 32-kDa inner-membrane protein that activates the ctx promoter in Escherichia coli and whose deletion in V. cholerae results in the inability to produce CT (5). Deletion analysis of the ctxAB promoter localized the binding site of ToxR to multiple heptad repeats, TTTTGAT, upstream of ctxAB (6). However, ToxR activation of ctxAB transcription in V. cholerae has not been demonstrated (7). Instead, ToxR in V. cholerae binds with its downstream enhancer ToxS to the upstream region of the toxT gene, which encodes another transcriptional activator (8). ToxT belongs to the AraC family of trans...

show abstract

“…efflux pumps (11,(27)(28)(29)(30)(31)(32)(33)(34). Efflux pumps are utilized by bacteria to expel antibiotics and other harmful substances from the bacterial cytosol.…”

Section: Figmentioning

confidence: 99%

Analysis of Shigella flexneri Resistance, Biofilm Formation, and Transcriptional Profile in Response to Bile Salts

et al. 2017

View full text Add to dashboard Cite

The Shigella species cause millions of cases of watery or bloody diarrhea each year, mostly in children in developing countries. While many aspects of Shigella colonic cell invasion are known, crucial gaps in knowledge regarding how the bacteria survive, transit, and regulate gene expression prior to infection remain. In this study, we define mechanisms of resistance to bile salts and build on previous research highlighting induced virulence in Shigella flexneri strain 2457T following exposure to bile salts. Typical growth patterns were observed within the physiological range of bile salts; however, growth was inhibited at higher concentrations. Interestingly, extended periods of exposure to bile salts led to biofilm formation, a conserved phenotype that we observed among members of the Enterobacteriaceae. Characterization of S. flexneri 2457T biofilms determined that both bile salts and glucose were required for formation, dispersion was dependent upon bile salts depletion, and recovered bacteria displayed induced adherence to HT-29 cells. RNAsequencing analysis verified an important bile salt transcriptional profile in S. flexneri 2457T, including induced drug resistance and virulence gene expression. Finally, functional mutagenesis identified the importance of the AcrAB efflux pump and lipopolysaccharide O-antigen synthesis for bile salt resistance. Our data demonstrate that S. flexneri 2457T employs multiple mechanisms to survive exposure to bile salts, which may have important implications for multidrug resistance. Furthermore, our work confirms that bile salts are important physiological signals to activate S. flexneri 2457T virulence. This work provides insights into how exposure to bile likely regulates Shigella survival and virulence during host transit and subsequent colonic infection.

show abstract

Effect of Bile on the Cell Surface Permeability Barrier and Efflux System of Vibrio cholerae

Cited by 52 publications

References 28 publications

Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump inCampylobacter jejuni

Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump inCampylobacter jejuni

Bile acids induce cholera toxin expression in Vibrio cholerae in a ToxT-independent manner

Analysis of Shigella flexneri Resistance, Biofilm Formation, and Transcriptional Profile in Response to Bile Salts

Contact Info

Product

Resources

About