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Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
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Developing multispecies quorum-sensing modulators based on the Streptococcus mitis competence-stimulating peptide.

Tahmina A Milly1, Clay P Renshaw1, Yftah Tal-Gan1

  • 1Department of Chemistry, University of Nevada, Reno, Reno, Nevada, USA.

The Journal of Biological Chemistry
|November 11, 2023
PubMed
Summary

We identified the competence-stimulating peptide (CSP) in Streptococcus mitis and developed novel quorum sensing (QS) modulators. These modulators target both S. mitis and Streptococcus pneumoniae, offering potential for multispecies bacterial infection control.

Keywords:
Streptococcus mitisStreptococcus pneumoniaeStructure-activity relationshipscompetence stimulating peptide (CSP)quorum sensing

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Area of Science:

  • Microbiology
  • Bacterial communication
  • Molecular biology

Background:

  • Quorum sensing (QS) regulates bacterial group behaviors and is a target for controlling infections without driving resistance.
  • Streptococcus mitis, a commensal, is a genetic reservoir for the pathogen Streptococcus pneumoniae.
  • The QS circuitry and its roles in S. mitis remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the competence regulon QS circuitry in S. mitis.
  • To identify the native CSP signal and its interaction mechanism with ComD.
  • To define the regulatory roles of QS in S. mitis phenotypes and develop QS modulators.

Main Methods:

  • Analysis of structure-activity relationships of CSP signals.
  • Development of novel CSP-based QS modulators.
  • Investigation of QS involvement in competence and biofilm formation.

Main Results:

  • Identified the native S. mitis CSP and its mechanism of ComD activation.
  • Revealed QS regulation of competence development and biofilm formation in S. mitis.
  • Developed a potent multispecies QS modulator targeting both S. mitis and S. pneumoniae.

Conclusions:

  • The competence regulon plays a key role in S. mitis phenotypes like competence and biofilm formation.
  • Novel CSP-based QS modulators were developed with potential for therapeutic applications.
  • Exploiting inter-species QS crosstalk offers a strategy for controlling related bacterial pathogens.