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- W4366988920 abstract "Abstract RavA-ViaA were reported to play a role in aminoglycoside sensitivity but the mechanisms remain elusive. Here, we performed competition and survival experiments to confirm that deletion of ravA-viaA increases tolerance of the Gram-negative pathogen Vibrio cholerae to low and high aminoglycoside concentrations, during aerobic growth. Using high throughput strategies in this species, we identify Cpx and Zra2 two-component systems as new partners of RavA-ViaA. We show that the aminoglycoside tolerance of Δravvia requires the presence of these membrane stress sensing two-component systems. We propose that deletion of the RavA-ViaA function facilitates the response aminoglycosides because of a pre-activated state of Cpx and Zra2 membrane stress response systems. We also find an impact of these genes on polymyxin B sensitivity and vancomycin resistance, and we show that simultaneous inactivation of ravvia function together with envelope stress response systems leads to outer membrane permeabilization. Vancomycin is mostly used for Gram-positive because of its low efficiency for crossing the Gram-negative outer membrane. Targeting of the ravA-viaA operon for inactivation could be a future strategy to allow uptake of vancomycin into multidrug resistant Gram-negative bacteria." @default.
- W4366988920 created "2023-04-27" @default.
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- W4366988920 date "2023-04-24" @default.
- W4366988920 modified "2023-10-02" @default.
- W4366988920 title "RavA-ViaA links<i>Vibrio cholerae</i>Cpx- and Zra2- envelope stress to antibiotic response" @default.
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- W4366988920 doi "https://doi.org/10.1101/2023.04.24.538083" @default.
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