Antibiotic-Induced Cell Chaining Triggers Pneumococcal Competence by Reshaping Quorum Sensing to Autocrine-Like Signaling.
Cell Rep, 2018/11/27;25(9):2390-2400.e3.
Domenech A[1], Slager J[2], Veening JW[3]
Affiliations
PMID: 30485808DOI: 10.1016/j.celrep.2018.11.007
Impact factor: 9.995
Abstract
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.
Keywords: CSP; Streptococcus pneumoniae; antibiotics; aztreonam; bacterial stress response; clavulanic acid; competence; contact-dependent signaling; quorum sensing; transformation
MeSH terms
Anti-Bacterial Agents; Autocrine Communication; Aztreonam; Bacterial Proteins; Clavulanic Acid; Gene Dosage; Gene Transfer, Horizontal; Models, Biological; Peptides; Quorum Sensing; Signal Transduction; Streptococcus pneumoniae
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