The BceABRS four-component system that is essential for cell envelope stress response is involved in sensing and response to host defence peptides and is required for the biofilm formation and fitness of Streptococcus mutans

Purpose. Streptococcus mutans is a primary cariogenic pathogen worldwide. In dental biofilms, S. mutans often faces life-threatening insults, such as killing by antimicrobial compounds from competing species and from the host. How such insults affect the physiology and virulence of S. mutans is poorly understood. In this study, we explored this question by investigating the responses of S. mutans strains to several host defence peptides and bacitracin. Methodology. S. mutans UA159 and its isogenic mutants, SmΔbceA, SmΔbceB, SmΔbceR and SmΔbceS, were examined for their antibiotic susceptibility and biofilm formation. The lux reporter strains were constructed to assay the responses of S. mutans to host defence peptides. In addition, the competitive fitness of these mutants against the parent in response to peptide antibiotics was determined in dual-strain mixed cultures. Results. S. mutans UA159 (WT) was generally insensitive to physiological concentrations of α-defensin-1, β-defensin-3, LL-37 and histatin-5, but all of the BceABRS mutants were sensitive to these peptide antibiotics. The response of S. mutans to these peptide antibiotics involved the transcriptional activation of the bceABRS operon itself. Bacitracin or β-defensin-3 at a sub-inhibitory concentration induced biofilm formation in the parent, but not in any of the BceABRS mutants. None of the mutants were able to compete with the parent for persistence in duel-strain cultures in the presence of bacitracin or β-defensin-3. Conclusion. The BceABRS four-component system in S. mutans is involved in sensing, response and resistance to host defence peptides, and is required for the biofilm formation and fitness of S. mutans.