TY - JOUR
T1 - Environmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway
AU - Do, Hackwon
AU - Makthal, Nishanth
AU - VanderWal, Arica R.
AU - Saavedra, Matthew Ojeda
AU - Olsen, Randall J.
AU - Musser, James M.
AU - Kumaraswami, Muthiah
N1 - Funding Information:
This work was supported by National Institutes of Health grant 1R01AI109096-01A1 to M.K. and funds from the Fondren Foundation to J.M.M. H.D. was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A03008353). Advanced Light Source was supported by Department of Energy contract DE-AC03-76SF00098.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/13
Y1 - 2019/6/13
N2 - 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.
AB - 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.
KW - Animals
KW - Bacterial Proteins/metabolism
KW - Disease Models, Animal
KW - Exotoxins/metabolism
KW - Female
KW - Gene Expression Regulation, Bacterial/physiology
KW - Histidine/metabolism
KW - Humans
KW - Hydrogen-Ion Concentration
KW - Mice
KW - Protein Sorting Signals/physiology
KW - Quorum Sensing/physiology
KW - Signal Transduction/physiology
KW - Streptococcal Infections/microbiology
KW - Streptococcus pyogenes/pathogenicity
KW - Virulence/physiology
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U2 - 10.1038/s41467-019-10556-8
DO - 10.1038/s41467-019-10556-8
M3 - Article
C2 - 31197146
AN - SCOPUS:85067345569
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2586
ER -