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

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

doi:10.1038/s41467-019-10556-8

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

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

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English (US)
Article number	2586
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10556-8
State	Published - Jun 13 2019

Keywords

Animals
Bacterial Proteins/metabolism
Disease Models, Animal
Exotoxins/metabolism
Female
Gene Expression Regulation, Bacterial/physiology
Histidine/metabolism
Humans
Hydrogen-Ion Concentration
Mice
Protein Sorting Signals/physiology
Quorum Sensing/physiology
Signal Transduction/physiology
Streptococcal Infections/microbiology
Streptococcus pyogenes/pathogenicity
Virulence/physiology

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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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.

In: Nature Communications, Vol. 10, No. 1, 2586, 13.06.2019.

Research output: Contribution to journal › Article › peer-review

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

Abstract

Keywords

ASJC Scopus subject areas

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