Differentially expressed genes in RND-efflux deficient V. cholerae. Vibrio cholerae strain:N16961

RND-family efflux systems are ubiquitous transporters that contribute to multiple antibiotic resistance in Gram negative bacteria. RND transporters also affect diverse phenotypes independent of their function in antibiotic resistance, suggesting that the RND systems fulfill unknown biological functions in Gram negative bacteria. However, the mechanisms by which RND efflux systems affect these phenotypes is unclear. Herein we show that the V. cholerae RND transporters maintain cell homeostasis by modulating the intracellular concentration of metabolites. When RND efflux is impaired, metabolites accumulate within the cell and stimulate environmental sensing systems to effect transcriptional responses and environmental adaptation. Our results suggest a novel paradigm for RND efflux transporters in bacterial sensing and responding to their environment.