Role of ToxS in the proteolytic cascade of virulence regulator ToxR in Vibrio cholerae

Molecular Microbiology
Salvador Almagro-MorenoR K Taylor

Abstract

Two of the primary virulence regulators of Vibrio cholerae, ToxR and TcpP, function together with cognate effector proteins. ToxR undergoes regulated intramembrane proteolysis (RIP) during late stationary phase in response to nutrient limitation at alkaline pH; however, the specific function of its cognate ToxS remains unresolved. In this work, we found that ToxR rapidly becomes undetectable in a ΔtoxS mutant when cultures are exposed to either starvation conditions or after alkaline pH shock individually. A ΔtoxS mutant enters into a dormant state associated with the proteolysis of ToxR at a faster rate than wild-type, closely resembling a ΔtoxR mutant. Using a mutant with a periplasmic substitution in ToxS, we found that the proteases DegS and DegP function additively with VesC and a novel protease, TapA, to degrade ToxR in the mutant. Overall, the results shown here reveal a role for ToxS in the stabilization of ToxR by protecting the virulence regulator from premature proteolysis.

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Citations

Jun 28, 2016·International Journal of Medical Microbiology : IJMM·Katharina PresslerStefan Schild
Mar 28, 2018·Journal of Bacteriology·S Nazmus SakibSalvador Almagro-Moreno
May 30, 2019·Journal of Bacteriology·Joshua D QuinnVirginia L Miller
Jun 17, 2020·Environmental Microbiology Reports·Jane M JayakumarSalvador Almagro-Moreno
Jan 10, 2018·Pathogens and Disease·Kenneth M Peterson, Patrick S Gellings
Jul 12, 2019·Frontiers in Cellular and Infection Microbiology·Nina PennetzdorferStefan Schild
May 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Troy P HubbardMatthew K Waldor
Nov 17, 2020·Frontiers in Molecular Biosciences·Sarah Wettstadt, María A Llamas
Jun 2, 2021·Journal of Bacteriology·Joshua D QuinnVirginia L Miller
Jul 27, 2021·Infection and Immunity·Yuding WengJames E Bina

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