Antibiotic-Induced Cell Chaining Triggers Pneumococcal Competence by Reshaping Quorum Sensing to Autocrine-Like Signaling
Antibiotic-Induced Cell Chaining Triggers Pneumococcal Competence by Reshaping Quorum Sensing to Autocrine-Like Signaling
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DOI：
10.1016/j.celrep.2018.11.007
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发表时间：
2018-11-27
期刊：
影响因子：
8.8
通讯作者：
Veening, Jan-Willem
中科院分区：
文献类型：
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作者：
Domenech, Arnau;Slager, Jelle;Veening, Jan-Willem
肺炎链球菌可以通过能力激活和随后的 DNA 摄取获得抗生素耐药性。在这里，我们证明氨曲南 (ATM) 和克拉维酸 (CLA) 可以提高能力。我们发现这两种化合物均通过靶向 D,D-羧肽酶 PBP3 来诱导细胞链形成。为了支持链形成促进能力的假设，我们证明自溶素突变体（Delta lytB）具有超能力。由于能力是通过小细胞外肽 (CSP) 与膜锚定受体 (ComD) 的结合启动的，因此我们想知道链的形成是否会改变 CSP 扩散动力学。事实上，ATM 或 CLA 的存在通过从全局群体感知转变为局部群体感知来影响能力同步，因为 CSP 主要保留在链式单元中，而不是在公共池中共享。重要的是，类自分泌信号传导延长了群体能够吸收 DNA 的时间窗口。这些见解共同证明了群体感应的多功能性，并强调了准确抗生素处方的重要性。
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 (Delta lytB) is hypercompetent. Since competence is initiated by the binding of a small extracellular peptide (CSP) to a membraneanchored 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.