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Cholera Toxin Production during Anaerobic Trimethylamine N-Oxide Respiration Is Mediated by Stringent Response in Vibrio cholerae

Authors
 Young Taek Oh  ;  Yongjin Park  ;  Mi Young Yoon  ;  Wasimul Bari  ;  Junhyeok Go  ;  Kyung Bae Min  ;  David M. Raskin  ;  Kang-Mu Lee  ;  Sang Sun Yoon 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(19) : 13232-13242, 2014 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2014
MeSH
Anaerobiosis/physiology ; Cholera Toxin/biosynthesis* ; Cholera Toxin/genetics ; Gene Deletion ; Methylamines/metabolism* ; Vibrio cholerae/genetics ; Vibrio cholerae/metabolism*
Keywords
Anaerobic Respiration ; Bacterial Pathogenesis ; Cholera Toxin ; Respiration ; Stress Response ; Stringent Response ; Vibrio cholerae ; Virulence Factors
Abstract
As a facultative anaerobe, Vibrio cholerae can grow by anaerobic respiration. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly promoted during anaerobic growth using trimethylamine N-oxide (TMAO) as an alternative electron acceptor. Here, we investigated the molecular mechanisms of TMAO-stimulated CT production and uncovered the crucial involvement of stringent response in this process. V. cholerae 7th pandemic strain N16961 produced a significantly elevated level of ppGpp, the bacterial stringent response alarmone, during anaerobic TMAO respiration. Bacterial viability was impaired, and DNA replication was also affected under the same growth condition, further suggesting that stringent response is induced. A ΔrelA ΔspoT ppGpp overproducer strain produced an enhanced level of CT, whereas anaerobic growth via TMAO respiration was severely inhibited. In contrast, a ppGpp-null strain (ΔrelA ΔspoT ΔrelV) grew substantially better, but produced no CT, suggesting that CT production and bacterial growth are inversely regulated in response to ppGpp accumulation. Bacterial capability to produce CT was completely lost when the dksA gene, which encodes a protein that works cooperatively with ppGpp, was deleted. In the ΔdksA mutant, stringent response growth inhibition was alleviated, further supporting the inverse regulation of CT production and anaerobic growth. In vivo virulence of ΔrelA ΔspoT ΔrelV or ΔdksA mutants was significantly attenuated. The ΔrelA ΔspoT mutant maintained virulence when infected with exogenous TMAO despite its defective growth. Together, our results reveal that stringent response is activated under TMAO-stimulated anaerobic growth, and it regulates CT production in a growth-dependent manner in V. cholerae.
Full Text
http://www.jbc.org/content/289/19/13232.long
DOI
10.1074/jbc.M113.540088
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Go, Jun Hyeok(고준혁)
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/22282913/98628
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