RT Journal Article
SR Electronic
T1 Antibiotic-induced cell chaining triggers pneumococcal competence by reshaping quorum sensing to autocrine-like signaling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 284125
DO 10.1101/284125
A1 Arnau Domenech
A1 Jelle Slager
A1 Jan-Willem Veening
YR 2018
UL http://biorxiv.org/content/early/2018/09/22/284125.abstract
AB 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 if chain formation alters CSP diffusion kinetics. Indeed, the presence of ATM or CLA 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 transform. Together, these insights demonstrate the versatility of quorum sensing and highlight the importance of an accurate antibiotic prescription.