Vibrio cholerae RND efflux systems: mediators of stress responses, colonization and pathogenesis

Abstract

Resistance Nodulation Division (RND) efflux systems are ubiquitous transporters in gram-negative bacteria that provide protection against antimicrobial agents and thereby enhance survival in virtually all environments these prokaryotes inhabit. Vibrio cholerae is a dual lifestyle enteric pathogen that spends much of its existence in aquatic environments. An unwitting encounter with a human host can lead to V. cholerae intestinal colonization by strains that encode cholera toxin and toxin co-regulated pilus virulence factors leading to potentially fatal cholera diarrhea and dissemination in the environment. Adaptive response mechanisms to host factors encountered by these pathogens are therefore critical both to engage survival mechanisms such as RND-mediated transporters and to induce timely expression of virulence factors. Sensing of cues encountered in the host may therefore activate more than protective responses such as efflux systems, but also be coordinated to initiate expression of virulence factors. This review summarizes recent advances that contribute towards the understanding of RND efflux physiological functions and how the transport systems interface with the regulation of virulence factor production in V. cholerae.

Iron-Fur complex suppresses the expression of components of the cyclo-(Phe-Pro)-signaling regulatory pathway in Vibrio vulnificus

“…The cFP-mediated QS pathway is also present in the human pathogen V. cholerae ( Park et al, 2006 ; Bina and Bina, 2010 ; Bina et al, 2013 ). In this pathogen, LeuO, which receives the cFP signal through ToxR similar to V. vulnificus , positively regulates the expression of ctxAB , the genes encoding the exotoxin cholera toxin, as well as ToxT, which induces the expression of various virulence-associated genes ( Silva and Benitez, 2016 ; Bhandari et al, 2021 ; Bina and Bina, 2023 ). To explore whether Fur-iron also regulates these genes involved in the cFP pathway in V. cholerae , we compared the transcription levels of leuO , toxT , and ctxAB in the V. cholerae O1 El Tor strain N16961 and its fur -deletion derivative using qRT-PCR.…”

A TetR family regulator of an RND efflux system that directs artemisinin resistance in Vibrio cholerae

“…Considering that VexR itself exerts positive regulation of the vexRAB operon, it needs to be further elucidated, which is the real sensor of ARS and/or other toxic chemicals such as erythromycin between AtrR and VexR. As in the case of the Cpx system that regulates both VexAB and VexGH systems in response to toxic metabolic by-products ( 15 ), it should be also noted that AtrR is another regulator that affects the expression of TolC, the only OEP commonly used for the other RND efflux systems, which is also under the control of CpxR ( 20 ). TolC is also required for the expression of the ToxR regulon, which is important for virulence potential in V. cholerae ( 21 ).…”