Nature Communications (Jul 2024)

Pneumococcal competence is a populational health sensor driving multilevel heterogeneity in response to antibiotics

  • Marc Prudhomme,
  • Calum H. G. Johnston,
  • Anne-Lise Soulet,
  • Anne Boyeldieu,
  • David De Lemos,
  • Nathalie Campo,
  • Patrice Polard

DOI
https://doi.org/10.1038/s41467-024-49853-2
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 15

Abstract

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Abstract Competence for natural transformation is a central driver of genetic diversity in bacteria. In the human pathogen Streptococcus pneumoniae, competence exhibits a populational character mediated by the stress-induced ComABCDE quorum-sensing (QS) system. Here, we explore how this cell-to-cell communication mechanism proceeds and the functional properties acquired by competent cells grown under lethal stress. We show that populational competence development depends on self-induced cells stochastically emerging in response to stresses, including antibiotics. Competence then propagates through the population from a low threshold density of self-induced cells, defining a biphasic Self-Induction and Propagation (SI&P) QS mechanism. We also reveal that a competent population displays either increased sensitivity or improved tolerance to lethal doses of antibiotics, dependent in the latter case on the competence-induced ComM division inhibitor. Remarkably, these surviving competent cells also display an altered transformation potential. Thus, the unveiled SI&P QS mechanism shapes pneumococcal competence as a health sensor of the clonal population, promoting a bet-hedging strategy that both responds to and drives cells towards heterogeneity.