Enhanced interaction of Vibrio cholerae virulence regulators TcpP and ToxR under oxygen-limiting conditions.
Vibrio cholerae is the causative agent of the diarrheal disease cholera. The ability of V. cholerae to colonize and cause disease requires the intricately regulated expression of a number of virulence factors during infection. One of the signals sensed by V. cholerae is the presence of oxygen-limiting conditions in the gut. It has been shown that the virulence activator AphB plays a key role in sensing low oxygen concentrations and inducing the transcription of another key virulence activator, TcpP. In this study, we used a bacterial two-hybrid system to further examine the effect of oxygen on different virulence regulators. We found that anoxic conditions enhanced the interaction between TcpP and ToxR, identified as the first positive regulator of V. cholerae virulence genes. We further demonstrated that the TcpP-ToxR interaction was dependent on the primary periplasmic protein disulfide formation enzyme DsbA and cysteine residues in the periplasmic domains of both ToxR and TcpP. Furthermore, we showed that in V. cholerae, an interaction between TcpP and ToxR is important for virulence gene induction. Under anaerobic growth conditions, we detected ToxR-TcpP heterodimers, which were abolished in the presence of the reducing agent dithiothreitol. Our results suggest that V. cholerae may sense intestinal anoxic signals by multiple components to activate virulence.
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Fenxia
F
Fan
Zhi
Z
Liu
Nusrat
N
Jabeen
L Dillon
LD
Birdwell
Jun
J
Zhu
Biao
B
Kan
D000693:Anaerobiosis / Q000502:physiology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000502:physiology*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C097244:TCPP protein, Vibrio cholerae; D014157:Transcription Factors; D037521:Virulence Factors; C499324:toxR protein, Vibrio cholerae