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Activation of cholera toxin production by anaerobic respiration of trimethylamine N-oxide in Vibrio cholerae

Authors
 Kang-Mu Lee  ;  Yongjin Park  ;  Wasimul Bari  ;  Mi Young Yoon  ;  Junhyeok Go  ;  Sang Cheol Kim  ;  Hyung-il Lee  ;  Sang Sun Yoon 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.287(47) : 39742-39752, 2012 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2012
MeSH
Amino Acid Substitution ; Anaerobiosis/drug effects ; Anaerobiosis/genetics ; Animals ; Bacterial Secretion Systems/drug effects ; Bacterial Secretion Systems/physiology* ; Cholera/enzymology* ; Cholera/genetics ; Cholera Toxin/genetics ; Cholera Toxin/secretion* ; Methylamines/pharmacology ; Mice ; Mutation, Missense ; Oxidants/pharmacology ; Periplasm/genetics ; Periplasm/secretion* ; Vibrio cholerae/enzymology* ; Vibrio cholerae/genetics ; Vibrio cholerae/pathogenicity ; Virulence Factors/genetics ; Virulence Factors/metabolism*
Keywords
Bacterial Pathogenesis ; Bacterial Toxins ; Cholera Toxin ; Respiration ; Virulence Factors ; Anaerobic Respiration ; Trimethylamine N-Oxide ; Vibrio Cholerae
Abstract
Vibrio cholerae is a gram-negative bacterium that causes cholera. Although the pathogenesis caused by this deadly pathogen takes place in the intestine, commonly thought to be anaerobic, anaerobiosis-induced virulence regulations are not fully elucidated. Anerobic growth of the V. cholerae strain, N16961, was promoted when trimethylamine N-oxide (TMAO) was used as an alternative electron acceptor. Strikingly, cholera toxin (CT) production was markedly induced during anaerobic TMAO respiration. N16961 mutants unable to metabolize TMAO were incapable of producing CT, suggesting a mechanistic link between anaerobic TMAO respiration and CT production. TMAO reductase is transported to the periplasm via the twin arginine transport (TAT) system. A similar defect in both anaerobic TMAO respiration and CT production was also observed in a N16961 TAT mutant. In contrast, the abilities to grow on TMAO and to produce CT were not affected in a mutant of the general secretion pathway. This suggests that V. cholerae may utilize the TAT system to secrete CT during TMAO respiration. During anaerobic growth with TMAO, N16961 cells exhibit green fluorescence when stained with 2',7'-dichlorofluorescein diacetate, a specific dye for reactive oxygen species (ROS). Furthermore, CT production was decreased in the presence of an ROS scavenger suggesting a positive role of ROS in regulating CT production. When TMAO was co-administered to infant mice infected with N16961, the mice exhibited more severe pathogenic symptoms. Together, our results reveal a novel anaerobic growth condition that stimulates V. cholerae to produce its major virulence factor.
Full Text
http://www.jbc.org/content/287/47/39742.long
DOI
23019319
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Yong Jin(박용진)
Yoon, Mi Young(윤미영)
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Lee, Kang Mu(이강무) ORCID logo https://orcid.org/0000-0001-7414-5921
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90627
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