TY - JOUR
T1 - The vibrio cholerae quorum-sensing protein VQMA integrates cell density, environmental, and host-derived cues into the control of virulence
AU - Mashruwala, Ameya A.
AU - Bassler, Bonnie L.
N1 - Funding Information:
We thank the Donia lab for generously allowing us to use their anaerobic chamber. We thank Ankur Dalia for the gift of protocols, strains, and reagents to facilitate MuGENT cloning. We thank Tharan Srikumar, Saw Kyin, and Henry Shwe for help with mass spectroscopy experiments. This work was supported by the Howard Hughes Medical Institute, National Science Foundation grant MCB-1713731, and NIH grant 5R37GM065859 to B.L.B. A.A.M. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Institute. The authors have no competing interests to declare.
Funding Information:
This work was supported by the Howard Hughes Medical Institute, National Science Foundation grant MCB-1713731, and NIH grant 5R37GM065859 to B.L.B. A.A.M. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Institute. The authors have no competing interests to declare.
Publisher Copyright:
© 2020 Mashruwala and Bassler.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Quorum sensing is a chemical communication process in which bacteria use the production, release, and detection of signal molecules called autoinducers to orchestrate collective behaviors. The human pathogen Vibrio cholerae requires quorum sensing to infect the small intestine. There, V. cholerae encounters the absence of oxygen and the presence of bile salts. We show that these two stimuli differentially affect quorum-sensing function and, in turn, V. cholerae pathogenicity. First, during anaerobic growth, V. cholerae does not produce the CAI-1 autoinducer, while it continues to produce the DPO autoinducer, suggesting that CAI-1 may encode information specific to the aerobic lifestyle of V. cholerae. Second, the quorum-sensing receptor-transcription factor called VqmA, which detects the DPO autoinducer, also detects the lack of oxygen and the presence of bile salts. Detection occurs via oxygen-, bile salt-, and redox-responsive disulfide bonds that alter VqmA DNA binding activity. We propose that VqmA serves as an information processing hub that integrates quorum-sensing information, redox status, the presence or absence of oxygen, and host cues. In response to the information acquired through this mechanism, V. cholerae appropriately modulates its virulence output. IMPORTANCE Quorum sensing (QS) is a process of chemical communication that bacteria use to orchestrate collective behaviors. QS communication relies on chemical signal molecules called autoinducers. QS regulates virulence in Vibrio cholerae, the causative agent of the disease cholera. Transit into the human small intestine, the site of cholera infection, exposes V. cholerae to the host environment. In this study, we show that the combination of two stimuli encountered in the small intestine, the absence of oxygen and the presence of host-produced bile salts, impinge on V. cholerae QS function and, in turn, pathogenicity. We suggest that possessing a QS system that is responsive to multiple environmental, host, and cell density cues enables V. cholerae to fine-tune its virulence capacity in the human intestine.
AB - Quorum sensing is a chemical communication process in which bacteria use the production, release, and detection of signal molecules called autoinducers to orchestrate collective behaviors. The human pathogen Vibrio cholerae requires quorum sensing to infect the small intestine. There, V. cholerae encounters the absence of oxygen and the presence of bile salts. We show that these two stimuli differentially affect quorum-sensing function and, in turn, V. cholerae pathogenicity. First, during anaerobic growth, V. cholerae does not produce the CAI-1 autoinducer, while it continues to produce the DPO autoinducer, suggesting that CAI-1 may encode information specific to the aerobic lifestyle of V. cholerae. Second, the quorum-sensing receptor-transcription factor called VqmA, which detects the DPO autoinducer, also detects the lack of oxygen and the presence of bile salts. Detection occurs via oxygen-, bile salt-, and redox-responsive disulfide bonds that alter VqmA DNA binding activity. We propose that VqmA serves as an information processing hub that integrates quorum-sensing information, redox status, the presence or absence of oxygen, and host cues. In response to the information acquired through this mechanism, V. cholerae appropriately modulates its virulence output. IMPORTANCE Quorum sensing (QS) is a process of chemical communication that bacteria use to orchestrate collective behaviors. QS communication relies on chemical signal molecules called autoinducers. QS regulates virulence in Vibrio cholerae, the causative agent of the disease cholera. Transit into the human small intestine, the site of cholera infection, exposes V. cholerae to the host environment. In this study, we show that the combination of two stimuli encountered in the small intestine, the absence of oxygen and the presence of host-produced bile salts, impinge on V. cholerae QS function and, in turn, pathogenicity. We suggest that possessing a QS system that is responsive to multiple environmental, host, and cell density cues enables V. cholerae to fine-tune its virulence capacity in the human intestine.
KW - Oxygen
KW - Pathogenesis
KW - Quorum sensing
KW - Redox
KW - Vibrio cholerae
KW - VqmA
UR - http://www.scopus.com/inward/record.url?scp=85088879422&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088879422&partnerID=8YFLogxK
U2 - 10.1128/mBio.01572-20
DO - 10.1128/mBio.01572-20
M3 - Article
C2 - 32723922
AN - SCOPUS:85088879422
SN - 2161-2129
VL - 11
SP - 1
EP - 19
JO - mBio
JF - mBio
IS - 4
M1 - e01572-20
ER -