Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland; Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands.
Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands.
Cell Rep. 2018 Nov 27;25(9):2390-2400.e3. doi: 10.1016/j.celrep.2018.11.007.
Streptococcus pneumoniae can acquire antibiotic resistance by activation of competence and subsequent DNA uptake. Here, we demonstrate that aztreonam (ATM) and clavulanic acid (CLA) promote competence. We show that both compounds induce cell chain formation by targeting the d,d-carboxypeptidase PBP3. In support of the hypothesis that chain formation promotes competence, we demonstrate that an autolysin mutant (ΔlytB) is hypercompetent. Since competence is initiated by the binding of a small extracellular peptide (CSP) to a membrane-anchored receptor (ComD), we wondered whether chain formation alters CSP diffusion kinetics. Indeed, ATM or CLA presence affects competence synchronization by shifting from global to local quorum sensing, as CSP is primarily retained to chained cells, rather than shared in a common pool. Importantly, autocrine-like signaling prolongs the time window in which the population is able to take up DNA. Together, these insights demonstrate the versatility of quorum sensing and highlight the importance of an accurate antibiotic prescription.
肺炎链球菌可以通过激活感受态和随后的 DNA 摄取获得抗生素耐药性。在这里，我们证明了氨曲南（ATM）和克拉维酸（CLA）促进感受态。我们表明，这两种化合物通过靶向 d,d-羧肽酶 PBP3 诱导细胞链形成。为了支持链形成促进感受态的假设，我们证明了一种自溶酶突变体（ΔlytB）具有超感受态。由于感受态是由小细胞外肽（CSP）与膜锚定受体（ComD）结合引发的，我们想知道链形成是否会改变 CSP 扩散动力学。事实上，ATM 或 CLA 的存在通过从全局到局部群体感应的转变来影响感受态同步，因为 CSP 主要保留在链状细胞中，而不是在公共池中共享。重要的是，自分泌样信号延长了种群能够摄取 DNA 的时间窗口。这些见解共同证明了群体感应的多功能性，并强调了准确的抗生素处方的重要性。
