title: Cholera Toxin Production Induced upon Anaerobic Respiration is Suppressed by Glucose Fermentation in Vibrio cholerae.
abstract: The causative agent of pandemic cholera, Vibrio cholerae, infects the anaerobic environment of the human intestine. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly induced during anaerobic respiration with trimethylamine N-oxide (TMAO) as an alternative electron acceptor. However, the molecular mechanism of TMAO-stimulated CT production is not fully understood. Herein, we reveal that CT production during anaerobic TMAO respiration is affected by glucose fermentation. When the seventh pandemic V. cholerae O1 strain N16961 was grown with TMAO and additional glucose, CT production was markedly reduced. Furthermore, an N16961 Δcrp mutant, devoid of cyclic AMP receptor protein (CRP), was defective in CT production during growth by anaerobic TMAO respiration, further suggesting a role of glucose metabolism in regulating TMAO-mediated CT production. TMAO reductase activity was noticeably decreased when grown together with glucose or by mutation of the crp gene. A CRP binding region was identified in the promoter region of the torD gene, which encodes a structural subunit of the TMAO reductase. Gel shift assays further confirmed the binding of purified CRP to the torD promoter sequence. Together, our results suggest that the bacterial ability to respire using TMAO is controlled by CRP, whose activity is dependent on glucose availability. Our results reveal a novel mechanism for the regulation of major virulence factor production by V. cholerae under anaerobic growth conditions.
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Oh
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Kang-Mu
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Brain Korea PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Wasimul
authors.initials: W
authors.lastname: Bari
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Brain Korea PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Brain Korea PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Brain Korea PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002771:Cholera / Q000382:microbiology*; D002772:Cholera Toxin / Q000378:metabolism*; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D002772:Cholera Toxin; D005947:Glucose
keywords: Anaerobic respiration; Cholera toxin; Glucose metabolism; Vibrio cholerae