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- W4200608743 abstract "Abstract Small multidrug resistance (SMR) transporters contribute to antibiotic resistance through proton-coupled efflux of toxic compounds from the bacterial cytoplasm. Previous biophysical studies of the E. coli SMR transporter EmrE suggested that it should also be capable of performing proton/toxin symport or uniport, leading to toxin susceptibility rather than resistance in vivo . Here we show EmrE does confer susceptibility to several newly characterized small-molecule substrates in E. coli , including harmane. In vitro experiments show that harmane binding to EmrE triggers uncoupled proton uniport and this protein-mediated dissipation of the transmembrane pH gradient underlies the in vivo phenotype. This leads to synergy with some existing antibiotics, such as kanamycin. Furthermore, this shows that it is possible to not just inhibit multidrug efflux but activate alternative transport modes that are detrimental to bacterial growth and metabolism." @default.
- W4200608743 created "2021-12-31" @default.
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- W4200608743 date "2021-12-05" @default.
- W4200608743 modified "2023-10-15" @default.
- W4200608743 title "Activating alternative transport modes in a multidrug resistance efflux pump to confer chemical susceptibility" @default.
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- W4200608743 doi "https://doi.org/10.1101/2021.12.04.471113" @default.
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