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Inhibition of the sodium-translocating NADH-ubiquinone oxidoreductase [Na⁺-NQR] decreases cholera toxin production in Vibrio cholerae O1 at the late exponential growth phase

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https://ir.library.oregonstate.edu/concern/articles/ng451k283

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  • Two virulence factors produced by Vibrio cholerae, cholera toxin (CT) and toxin-corregulated pilus (TCP), are indispensable for cholera infection. ToxT is the central regulatory protein involved in activation of CT and TCP expression. We previously reported that lack of a respiration-linked sodium-translocating NADH–ubiquinone oxidoreductase (Na⁺-NQR) significantly increases toxT transcription. In this study, we further characterized this link and found that Na⁺-NQR affects toxT expression only at the early-log growth phase, whereas lack of Na⁺-NQR decreases CT production after the mid-log growth phase. Such decreased CT production was independent of toxT and ctxB transcription. Supplementing a respiratory substrate, L-lactate, into the growth media restored CT production in the nqrA-F mutant, suggesting that decreased CT production in the Na⁺-NQR mutant is dependent on electron transport chain (ETC) activity. This notion was supported by the observations that two chemical inhibitors, a Na⁺-NQR specific inhibitor 2-n-Heptyl-4-hydroxyquinoline N-oxide (HQNO) and a succinate dehydrogenase (SDH) inhibitor, thenoyltrifluoroacetone (TTFA), strongly inhibited CT production in both classical and El Tor biotype strains of V. cholerae. Accordingly, we propose the main respiratory enzyme of V. cholerae, as a potential drug target to treat cholera because human mitochondria do not contain Na⁺-NQR orthologs.
  • Keywords: Anti-virulence drug, Electron transport chain, Na⁺-NQR, Vibrio cholerae, Cholera toxin
  • Keywords: Anti-virulence drug, Electron transport chain, Na⁺-NQR, Vibrio cholerae, Cholera toxin
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  • Minato, Y., Fassio, S. R., Reddekopp, R. L., & Häse, C. C. (2014). Inhibition of the sodium-translocating NADH-ubiquinone oxidoreductase [Na+-NQR] decreases cholera toxin production in Vibrio cholerae 01 at the late exponential growth phase. Microbial Pathogenesis, 66, 36-39. doi:10.1016/j.micpath.2013.12.002
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  • 66
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  • This research was supported by grants from the National Institutes of Health to C.C.H. [AI-063121-02]. S.R.F was partially supported by the OSU Undergraduate Research, Innovation, Scholarship & Creativity (URISC) fund and the OSU Howard Hughes Medical Institute Summer Undergraduate Research Program.
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