Mechanism for inhibition of Vibrio cholerae ToxT activity by the unsaturated fatty acid components of bile

Journal of Bacteriology
Sarah C Plecha, Jeffrey H Withey

Abstract

The Gram-negative curved bacillus Vibrio cholerae causes the severe diarrheal illness cholera. During host infection, a complex regulatory cascade results in production of ToxT, a DNA-binding protein that activates the transcription of major virulence genes that encode cholera toxin (CT) and toxin-coregulated pilus (TCP). Previous studies have shown that bile and its unsaturated fatty acid (UFA) components reduce virulence gene expression and therefore are likely important signals upon entering the host. However, the mechanism for the bile-mediated reduction of TCP and CT expression has not been clearly defined. There are two likely hypotheses to explain this reduction: (i) UFAs decrease DNA binding by ToxT, or (ii) UFAs decrease dimerization of ToxT. The work presented here elucidates that bile or UFAs directly affect DNA binding by ToxT. UFAs, specifically linoleic acid, can enter V. cholerae when added exogenously and are present in the cytoplasm, where they can then interact with ToxT. Electrophoretic mobility shift assays (EMSAs) with ToxT and various virulence promoters in the presence or absence of UFAs showed a direct reduction in ToxT binding to DNA, even in promoters with only one ToxT binding site. Virstatin, a synth...Continue Reading

References

May 29, 1987·Clinica Chimica Acta; International Journal of Clinical Chemistry·G P van Berge HenegouwenA T Ruben
Jan 1, 1972·Molecular & General Genetics : MGG·F B HaugliA Jimenez
Jan 1, 1972·Molecular & General Genetics : MGG·R C Gethmann
Oct 1, 1994·Molecular Microbiology·D E Higgins, V J DiRita
Mar 1, 1997·Infection and Immunity·S Gupta, R Chowdhury
Nov 14, 1997·Molecular Microbiology·K Skorupski, R K Taylor
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·C C Häse, J J Mekalanos
Feb 27, 1999·Journal of Bacteriology·D A Schuhmacher, K E Klose
Aug 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·D Provenzano, K E Klose
Jun 13, 2001·Infection and Immunity·J E Bina, J J Mekalanos
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Sep 25, 2002·Journal of Bacteriology·Robin R Hulbert, Ronald K Taylor
Oct 7, 2004·Journal of Bacteriology·Arpita ChatterjeeRukhsana Chowdhury
Feb 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Deborah T Hung, John J Mekalanos
Nov 3, 2005·Molecular Microbiology·Michael G ProutyKarl E Klose
Nov 18, 2005·Journal of Bacteriology·Jeffrey H Withey, Victor J Dirita
Mar 24, 2006·Molecular Microbiology·Jeffrey H Withey, Victor J DiRita
Feb 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth A ShakhnovichJohn J Mekalanos
Jul 1, 2009·Infection and Immunity·Basel H Abuaita, Jeffrey H Withey
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael J LowdenF Jon Kull
Mar 31, 2012·Bulletin of the World Health Organization·Mohammad AliJohn Clemens
Jul 24, 2012·Journal of Bacteriology·Jennifer B Dittmer, Jeffrey H Withey
Sep 4, 2014·Journal of Bacteriology·Joshua J Thomson, Jeffrey H Withey

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Citations

Feb 6, 2016·PLoS Neglected Tropical Diseases·Anisia J Silva, Jorge A Benitez
Mar 24, 2017·Scientific Reports·Anne K WoodbreyF Jon Kull
Oct 5, 2017·Future Microbiology·Birgitte H Kallipolitis
Nov 20, 2015·Basic & Clinical Pharmacology & Toxicology·Douglas S CostaJand Venes R Medeiros
Nov 17, 2016·Infection and Immunity·Amanda J HayJun Zhu
Sep 24, 2015·Antimicrobial Agents and Chemotherapy·Jeffrey H WitheyHemanta Koley
Jun 26, 2018·Angewandte Chemie·Markus LakemeyerStephan A Sieber
Feb 21, 2018·Future Medicinal Chemistry·Andrés GonzálezÁngel Lanas
Aug 2, 2020·The Journal of Pharmacy and Pharmacology·Francisca B M SousaJand V R Medeiros
Feb 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Eun Jin KimDong Wook Kim
Jan 10, 2018·Pathogens and Disease·Kenneth M Peterson, Patrick S Gellings
Oct 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Reed PiferVanessa Sperandio
May 13, 2020·Journal of Bacteriology·Patrícia T Dos SantosBirgitte H Kallipolitis
Jun 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Geoffrey B SeverinWai-Leung Ng
Jul 12, 2019·Frontiers in Cellular and Infection Microbiology·Nina PennetzdorferStefan Schild
Apr 23, 2020·Science Signaling·María Ayelén CarabajalEleonora García Véscovi
Jul 29, 2016·Clinical Microbiology Reviews·Jeticia R SistrunkChristina S Faherty
Jun 3, 2017·ACS Central Science·Shentian ZhuangXiaoguang Lei
Jul 7, 2021·Journal of Bacteriology·Jennifer B Stone, Jeffrey H Withey
Sep 21, 2021·Infection and Immunity·Thomas F BinaJames E Bina

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