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Proteolysis of ToxR is controlled by cysteine‐thiol redox state and bile salts in Vibrio cholerae
Author(s) -
Lembke Mareike,
Pennetzdorfer Nina,
Tutz Sarah,
Koller Michael,
Vorkapic Dina,
Zhu Jun,
Schild Stefan,
Reidl Joachim
Publication year - 2018
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14125
Subject(s) - proteolysis , biology , periplasmic space , vibrio cholerae , proteases , biochemistry , cysteine , transcription factor , transmembrane protein , microbiology and biotechnology , enzyme , gene , receptor , escherichia coli , genetics , bacteria
Summary In Vibrio cholerae , virulence gene expression is regulated by a transmembrane‐localized transcription factor complex designated as ToxRS. ToxR harbours two cysteines in the periplasmic domain that can form inter‐ and intramolecular disulfide bonds. In this study, we investigated the σ E ‐dependent inner membrane proteolysis of ToxR, which occurs via the periplasmic‐localized proteases DegS and DegP. Both proteases respond to the redox state of the two cysteine thiol groups of ToxR. Interestingly, in the presence of sodium deoxycholate, ToxR proteolysis is blocked independently of ToxS, whereas ToxR activation by bile salts requires ToxS function. From these data, we identified at least two levels of control for ToxR activation by sodiumdeoxycholate. First, bile inhibits ToxR degradation under starvation and alkaline pH or under conditions in which DegPS responds to the reduced disulfide bonds of ToxR. The second level links bile to ToxRS complex formation and further activation of its transcription factor activity. Overall, our data suggest a comprehensive bile sensory function for the ToxRS complex during host colonization.