Matches in SemOpenAlex for { <https://semopenalex.org/work/W2615062474> ?p ?o ?g. }
- W2615062474 abstract "ABSTRACT Resistance-nodulation-division (RND) superfamily efflux systems have been widely studied for their role in antibiotic resistance, but their native biological functions remain poorly understood. We previously showed that loss of RND-mediated efflux in Vibrio cholerae resulted in activation of the Cpx two-component regulatory system, which mediates adaptation to stress resulting from misfolded membrane proteins. Here, we investigated the mechanism linking RND-mediated efflux to the Cpx response. We performed transposon mutagenesis screening of RND-deficient V. cholerae to identify Cpx suppressors. Suppressor mutations mapped to genes involved in the biosynthesis of the catechol siderophore vibriobactin. We subsequently demonstrated that vibriobactin secretion is impaired in mutants lacking the VexGH RND efflux system and that impaired vibriobactin secretion is responsible for Cpx system activation, suggesting that VexGH secretes vibriobactin. This conclusion was bolstered by results showing that vexGH expression is induced by iron limitation and that vexH -deficient cells exhibit reduced fitness during growth under iron-limiting conditions. Our results support a model where VexGH contributes to cellular homeostasis by effluxing vibriobactin. In the absence of vexGH , retained vibriobactin appears to chelate iron from iron-rich components of the respiratory chain, with the deferrated proteins functioning to activate the Cpx response. Our collective results demonstrate that a native function of the V. cholerae VexGH RND efflux system is in vibriobactin secretion and that vibriobactin efflux is critical for maintenance of cellular homeostasis. IMPORTANCE RND efflux systems are ubiquitous Gram-negative transporters that play critical roles in antimicrobial resistance. In addition to antimicrobial resistance, RND transporters also affect the expression of diverse phenotypes, including virulence, cell metabolism, and stress responses. The latter observations suggest that RND transporters fulfill unknown physiological functions in the cell independently of their role in antimicrobial resistance. Vibrio cholerae is representative of many Gram-negative bacteria in encoding multiple RND transporters that are redundant in antimicrobial resistance and affect multiple phenotypes. Here we describe a novel function of the V. cholerae VexGH RND transporter in vibriobactin secretion. We show that vibriobactin production in VexGH-deficient cells impacts cell homeostasis, leading to activation of the Cpx stress response and reduced fitness under iron-limiting conditions. Our results highlight a native physiological function of an RND transporter and provide insight into the selective forces that maintain what was thought to be a redundant multidrug transporter." @default.
- W2615062474 created "2017-05-26" @default.
- W2615062474 creator A5012207697 @default.
- W2615062474 creator A5015588400 @default.
- W2615062474 creator A5029710135 @default.
- W2615062474 date "2017-07-05" @default.
- W2615062474 modified "2023-10-01" @default.
- W2615062474 title "The <i>Vibrio cholerae</i> VexGH RND Efflux System Maintains Cellular Homeostasis by Effluxing Vibriobactin" @default.
- W2615062474 cites W1505758906 @default.
- W2615062474 cites W1531182450 @default.
- W2615062474 cites W1587329961 @default.
- W2615062474 cites W1747389599 @default.
- W2615062474 cites W1787690277 @default.
- W2615062474 cites W1915801507 @default.
- W2615062474 cites W1939312344 @default.
- W2615062474 cites W1943555456 @default.
- W2615062474 cites W1960351290 @default.
- W2615062474 cites W1961907437 @default.
- W2615062474 cites W1966223820 @default.
- W2615062474 cites W1970632274 @default.
- W2615062474 cites W1971794548 @default.
- W2615062474 cites W1977565076 @default.
- W2615062474 cites W1999979510 @default.
- W2615062474 cites W2005736754 @default.
- W2615062474 cites W2009491450 @default.
- W2615062474 cites W2013740990 @default.
- W2615062474 cites W2014723793 @default.
- W2615062474 cites W2019045057 @default.
- W2615062474 cites W2021907449 @default.
- W2615062474 cites W2029956246 @default.
- W2615062474 cites W2030015794 @default.
- W2615062474 cites W2036205382 @default.
- W2615062474 cites W2038545761 @default.
- W2615062474 cites W2044414180 @default.
- W2615062474 cites W2044678473 @default.
- W2615062474 cites W2047232974 @default.
- W2615062474 cites W2068190050 @default.
- W2615062474 cites W2096629830 @default.
- W2615062474 cites W2101948177 @default.
- W2615062474 cites W2104192645 @default.
- W2615062474 cites W2108654063 @default.
- W2615062474 cites W2109809698 @default.
- W2615062474 cites W2110344351 @default.
- W2615062474 cites W2110830984 @default.
- W2615062474 cites W2112634425 @default.
- W2615062474 cites W2113254135 @default.
- W2615062474 cites W2115023451 @default.
- W2615062474 cites W2122086668 @default.
- W2615062474 cites W2135414906 @default.
- W2615062474 cites W2139152590 @default.
- W2615062474 cites W2139459279 @default.
- W2615062474 cites W2140441351 @default.
- W2615062474 cites W2140829667 @default.
- W2615062474 cites W2142424488 @default.
- W2615062474 cites W2145210590 @default.
- W2615062474 cites W2149460060 @default.
- W2615062474 cites W2149790826 @default.
- W2615062474 cites W2156073142 @default.
- W2615062474 cites W2160084442 @default.
- W2615062474 cites W2164485511 @default.
- W2615062474 cites W2166616050 @default.
- W2615062474 cites W2168749488 @default.
- W2615062474 cites W2168894173 @default.
- W2615062474 cites W4245742040 @default.
- W2615062474 cites W7827006 @default.
- W2615062474 doi "https://doi.org/10.1128/mbio.00126-17" @default.
- W2615062474 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5433094" @default.
- W2615062474 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28512090" @default.
- W2615062474 hasPublicationYear "2017" @default.
- W2615062474 type Work @default.
- W2615062474 sameAs 2615062474 @default.
- W2615062474 citedByCount "31" @default.
- W2615062474 countsByYear W26150624742017 @default.
- W2615062474 countsByYear W26150624742018 @default.
- W2615062474 countsByYear W26150624742019 @default.
- W2615062474 countsByYear W26150624742020 @default.
- W2615062474 countsByYear W26150624742021 @default.
- W2615062474 countsByYear W26150624742022 @default.
- W2615062474 countsByYear W26150624742023 @default.
- W2615062474 crossrefType "journal-article" @default.
- W2615062474 hasAuthorship W2615062474A5012207697 @default.
- W2615062474 hasAuthorship W2615062474A5015588400 @default.
- W2615062474 hasAuthorship W2615062474A5029710135 @default.
- W2615062474 hasBestOaLocation W26150624741 @default.
- W2615062474 hasConcept C104317684 @default.
- W2615062474 hasConcept C108319773 @default.
- W2615062474 hasConcept C143065580 @default.
- W2615062474 hasConcept C149011108 @default.
- W2615062474 hasConcept C16318435 @default.
- W2615062474 hasConcept C200082930 @default.
- W2615062474 hasConcept C2778643871 @default.
- W2615062474 hasConcept C44312359 @default.
- W2615062474 hasConcept C49039625 @default.
- W2615062474 hasConcept C51785407 @default.
- W2615062474 hasConcept C523546767 @default.
- W2615062474 hasConcept C54355233 @default.
- W2615062474 hasConcept C55493867 @default.
- W2615062474 hasConcept C86803240 @default.
- W2615062474 hasConcept C89423630 @default.
- W2615062474 hasConcept C95444343 @default.