title: Conjugated Linoleic Acid Reduces Cholera Toxin Production In Vitro and In Vivo by Inhibiting Vibrio cholerae ToxT Activity.
abstract: The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of V. cholerae virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA jwithey@med.wayne.edu.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Withey
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Dhrubajyoti
authors.initials: D
authors.lastname: Nag
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Plecha
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Ritam
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Hemanta
authors.initials: H
authors.lastname: Koley
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002771:Cholera / Q000188:drug therapy / Q000503:physiopathology; D002772:Cholera Toxin / Q000096:biosynthesis* / Q000235:genetics; D004269:DNA, Bacterial / Q000378:metabolism; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D011817:Rabbits; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D044243:Linoleic Acids, Conjugated; D014157:Transcription Factors; D037521:Virulence Factors; C075626:tcpN protein, Vibrio cholerae; D002772:Cholera Toxin