Fighting the spread of antibiotic resistance with bacterial competence inhibitors

Streptococcus pneumoniae is a commensal of the human nasopharynx, but it can also cause severe life-threatening antibiotic-resistant infections. Antibiotic consumption drives the spread of resistance by inducing S. pneumoniae competence leading to the uptake of exogenous DNA and horizontal gene transfer (HGT). We have identified potent inhibitors of competence, collectively called COM-blockers. We show that COM-blockers inhibit HGT by perturbing the proton motive force, thereby disrupting the export of the peptide that regulates competence. COM-blockers do not affect growth or compromise antibiotic activity at their active concentrations, and we did not observe any resistance development against them. Used as adjuvants of antibiotics, COM-blockers provide a strategy to reduce the spread of virulence factors and antibiotic resistance in human pathogens.