Redox pathway sensing bile salts activates virulence gene expression in Vibrio cholerae.
Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, has evolved signal transduction systems to control co-ordinately the expression of virulence determinants. It was previously shown that the presence of the bile salts glycocholate and taurocholate in the small intestine causes dimerization of the transmembrane transcription factor TcpP by inducing intermolecular disulphide bonds in the TcpP periplasmic domain. In this study, they further investigated the mechanism of how taurocholate affects V. cholerae virulence determinants. In vitro assay of TcpP oxidation by VcDsbA showed that VcDsbA induced TcpP dimerization in the presence of taurocholate. Taurocholate bound to VcDsbA with a KDof 40 ± 2.5 μM, and also bound other Dsb proteins, including EcDsbA, EcDsbC and VcDsbC. Taurocholate inhibited VcDsbA reductase activity without affecting VcDsbA secondary structure or thermostability. VcDsbA and its substrates were more extensively reduced in the presence of taurocholate, as compared with their redox state in the absence of taurocholate. The data presented here not only provide new insights into the mechanism by which bile salts induce V. cholerae virulence but also suggest a means by which to develop inhibitors against DsbA.
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.
Yuanyuan
Y
Xue
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.
Fei
F
Tu
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.
Mengting
M
Shi
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.|Department of Animal Science, Wenzhou Vocational College of Science and Technology, Wenzhou, Zhejiang, China.
Chun-Qin
CQ
Wu
New England Biolabs Inc, Ipswich, Massachusetts, USA.
Guoping
G
Ren
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.
Xiaojie
X
Wang
Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Weihuan
W
Fang
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.
Houhui
H
Song
College of Animal Science & Technology, China-Australia Joint-Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin'an 311300, Zhejiang Province, China.
Menghua
M
Yang
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D013656:Taurocholic Acid / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D037521:Virulence Factors; D013656:Taurocholic Acid; D010088:Oxidoreductases