Laboratoire de Microbiologie et Génétique Moléculaires (LMGM), UMR5100, Centre de Biologie Intégrative (CBI), Centre Nationale de la Recherche Scientifique (CNRS), Toulouse, France.
Université Paul Sabatier (Toulouse III), Toulouse, France.
Nat Commun. 2024 Jul 10;15(1):5625. doi: 10.1038/s41467-024-49853-2.
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.
自然转化能力是细菌遗传多样性的核心驱动力。在人类病原体肺炎链球菌中，由应激诱导的 ComABCDE 群体感应 (QS) 系统介导，表现出种群特征。在这里，我们探讨了这种细胞间通讯机制的进展以及在致死应激下生长的感受态细胞获得的功能特性。我们表明，种群感受态的发展取决于对包括抗生素在内的应激随机出现的自我诱导细胞。然后，感受态从自我诱导细胞的低阈值密度开始在种群中传播，定义了一个双相自我诱导和传播 (SI&P) QS 机制。我们还揭示了一个感受态群体对致死剂量的抗生素表现出要么更高的敏感性，要么更好的耐受性，在后一种情况下，这取决于感受态诱导的 ComM 分裂抑制剂。值得注意的是，这些存活的感受态细胞也表现出改变的转化潜力。因此，揭示的 SI&P QS 机制将肺炎球菌的感受态塑造为克隆种群的健康传感器，促进了一种既能对细胞做出反应又能促使细胞向异质性发展的风险分担策略。
