Environmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway

Do, Hackwon; Makthal, Nishanth; VanderWal, Arica R.; Saavedra, Matthew Ojeda; Olsen, Randall J.; Musser, James M.; Kumaraswami, Muthiah

doi:10.1038/s41467-019-10556-8

Title: Environmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway

Journal Article · Thu Jun 13 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-10556-8· OSTI ID:1624160

Do, Hackwon ^[1]; Makthal, Nishanth ^[2]; VanderWal, Arica R. ^[2]; Saavedra, Matthew Ojeda ^[2]; Olsen, Randall J. ^[3]; Musser, James M. ^[4];

^[5]

Houston Methodist Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Research Institute, Houston, TX (United States). Dept. of Pathology and Genomic Medicine
Houston Methodist Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Research Institute, Houston, TX (United States). Dept. of Pathology and Genomic Medicine
Houston Methodist Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Research Institute, Houston, TX (United States). Dept. of Pathology and Genomic Medicine; Weill Medical College of Cornell University, New York, NY (United States). Dept. of Pathology and Laboratory Medicine
Houston Methodist Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Research Institute, Houston, TX (United States). Dept. of Pathology and Genomic Medicine; Weill Medical College of Cornell University, New York, NY (United States). Dept. of Pathology and Laboratory Medicine
Houston Methodist Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Research Institute, Houston, TX (United States). Dept. of Pathology and Genomic Medicine

Bacteria control gene expression in concert with their population density by a process called quorum sensing, which is modulated by bacterial chemical signals and environmental factors. In the human pathogen Streptococcus pyogenes, production of secreted virulence factor SpeB is controlled by a quorum-sensing pathway and environmental pH. The quorum-sensing pathway consists of a secreted leaderless peptide signal (SIP), and its cognate receptor RopB. Here, we report that the SIP quorum-sensing pathway has a pH-sensing mechanism operative through a pH-sensitive histidine switch located at the base of the SIP-binding pocket of RopB. Environmental acidification induces protonation of His144 and reorganization of hydrogen bonding networks in RopB, which facilitates SIP recognition. The convergence of two disparate signals in the SIP signaling pathway results in induction of SpeB production and increased bacterial virulence. Our findings provide a model for investigating analogous crosstalk in other microorganisms.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); National Research Foundation of Korea, Ministry of Education

Grant/Contract Number:: AC03-76SF00098; 1R01AI109096-01A1; 2017R1A6A3A03008353

OSTI ID:: 1624160

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 28 works

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