Antibiotic-Induced Cell Chaining Triggers Pneumococcal Competence by Reshaping Quorum Sensing to Autocrine-Like Signaling

• Published in: Cell reports (Cambridge) 2018-11, Vol.25 (9), p.2390-2400.e3
• Main Authors: Domenech, Arnau, Slager, Jelle, Veening, Jan-Willem
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; antibiotics; Autocrine Communication - drug effects; aztreonam; Aztreonam - pharmacology; Bacterial Proteins - metabolism; bacterial stress response; clavulanic acid; Clavulanic Acid - pharmacology; competence; contact-dependent signaling; CSP; Gene Dosage; Gene Transfer, Horizontal - genetics; Models, Biological; Peptides - metabolism; quorum sensing; Quorum Sensing - drug effects; Signal Transduction - drug effects; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - physiology; transformation
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •Identification of a mechanism by which antibiotics induce competence in S. pneumoniae•Antibiotics targeting penicillin-binding protein 3 promote chain formation•Cell chains retain, rather than diffuse, the quorum-sensing peptide CSP•Chaining populations feature a longer competence and transformation time window Streptococcus pneumoniae can take up exogenous DNA by activating competence. Aztreonam and clavulanic acid can induce competence by targeting PBP3, leading to cell chaining. Cell chaining reshapes quorum sensing to autocrine-like signaling and increases the time window in which cells can take up DNA, potentially accelerating the spread of antibiotic resistance.