A Sub-population of Group A Streptococcus Elicits a Population-wide Production of Bacteriocins to Establish Dominance in the Host

Baruch B. Hertzog, Yael Kaufman, Debabrata Biswas, Miriam Ravins, Poornima Ambalavanan, Reuven Wiener, Veronique Angeli, Swaine L. Chen, Emanuel Hanski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Bacteria use quorum sensing (QS) to regulate gene expression. We identified a group A Streptococcus (GAS) strain possessing the QS system sil, which produces functional bacteriocins, through a sequential signaling pathway integrating host and bacterial signals. Host cells infected by GAS release asparagine (ASN), which is sensed by the bacteria to alter its gene expression and rate of proliferation. We show that upon ASN sensing, GAS upregulates expression of the QS autoinducer peptide SilCR. Initial SilCR expression activates the autoinduction cycle for further SilCR production. The autoinduction process propagates throughout the GAS population, resulting in bacteriocin production. Subcutaneous co-injection of mice with a bacteriocin-producing strain and the globally disseminated M1T1 GAS clone results in M1T1 killing within soft tissue. Thus, by sensing host signals, a fraction of a bacterial population can trigger an autoinduction mechanism mediated by QS, which acts on the entire bacterial community to outcompete other bacteria within the infection. Pathogenic bacteria evolved exquisite systems to sense their hosts and adjust their responses to ensure their survival and propagation. Hertzog, Kaufman et al. report that GAS produces bacteriocins through a sequential signaling pathway, integrating host and bacterial signals. Bacteriocins kill other bacteria within the infection, enabling GAS to establish dominance.

Original languageAmerican English
Pages (from-to)312-323.e6
JournalCell Host and Microbe
Volume23
Issue number3
DOIs
StatePublished - 14 Mar 2018

Bibliographical note

Funding Information:
This work was supported by grants from The Israeli Science Foundation administered by the Israel Academy of Science and Humanities (grants 295/17 , 2266/15 , 507/13 ) and by the National Research Foundation , Prime Minister's Office, Singapore under its Campus of Research Excellence and Technological Enterprise (CREATE) program (to E.H.). S.L.C. and some of the sequencing analysis were supported by the Singapore Ministry of Health's National Medical Research Council under its Clinician-Scientist Individual Research Grant ( NMRC/CIRG/1357/2013 ) (to S.L.C.). We thank John K. McCormick for providing us with detailed protocols for the expression and purification of bacteriocins and for the soft agar bacteriocin-mediated killing assay.

Funding Information:
This work was supported by grants from The Israeli Science Foundation administered by the Israel Academy of Science and Humanities (grants 295/17, 2266/15, 507/13) and by the National Research Foundation, Prime Minister's Office, Singapore under its Campus of Research Excellence and Technological Enterprise (CREATE) program (to E.H.). S.L.C. and some of the sequencing analysis were supported by the Singapore Ministry of Health's National Medical Research Council under its Clinician-Scientist Individual Research Grant (NMRC/CIRG/1357/2013) (to S.L.C.). We thank John K. McCormick for providing us with detailed protocols for the expression and purification of bacteriocins and for the soft agar bacteriocin-mediated killing assay.

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • asparagine
  • bacteriocins
  • group A Streptococcus
  • host sensing
  • micro-colonies
  • quorum sensing
  • sil
  • soft tissues
  • virulence

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