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

Yusuke Minato, Sara R. Fassio, Rylan L. Reddekopp, Claudia C. Häse

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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 CTand 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.

Original languageEnglish
Pages (from-to)36-39
Number of pages4
JournalMicrobial Pathogenesis
Volume66
DOIs
Publication statusPublished - 01-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Inhibition of the sodium-translocating NADH-ubiquinone oxidoreductase [Na<sup>+</sup>-NQR] decreases cholera toxin production in Vibrio cholerae O1 at the late exponential growth phase'. Together they form a unique fingerprint.

Cite this