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 <i>Streptococcus mutans</i>.
Tian. Xiao-Lin XL; Salim. Hasan H; Dong. Gaofeng G; Parcells. Madison M; Li. Yung-Hua YH
Key Findings
- Wild‑type S. mutans is resistant to physiological levels of LL‑37, α‑defensin‑1, β‑defensin‑3, and histatin‑5.
- The BceABRS four‑component system is required for this resistance; mutants lacking any part of the system become sensitive to the peptides.
- Sub‑inhibitory concentrations of LL‑37 or bacitracin trigger increased biofilm formation in the wild‑type strain, but not in the BceABRS mutants.
Practical Outcomes
- For DIY health enthusiasts, this means that using LL‑37 as an oral antimicrobial is unlikely to kill S. mutans and may even encourage biofilm (plaque) formation at low doses. The findings do not support LL‑37 as a useful supplement for preventing cavities or improving oral health.
Summary
The study shows that the tooth‑decay bacterium Streptococcus mutans can normally survive the human antimicrobial peptide LL‑37 thanks to a special four‑gene system (BceABRS). When this system is broken, the bacteria become sensitive to LL‑37 and other host peptides, but the normal bacteria actually use low levels of these peptides to make stronger biofilms.
Abstract
<b>Purpose.</b> <i>Streptococcus mutans</i> is a primary cariogenic pathogen worldwide. In dental biofilms, <i>S. mutans</i> 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 <i>S. mutans</i> is poorly understood. In this study, we explored this question by investigating the responses of <i>S. mutans</i> strains to several host defence peptides and bacitracin.<b>Methodology.</b> <i>S. mutans</i> UA159 and its isogenic mutants, SmΔbceA, SmΔbceB, SmΔbceR and SmΔbceS, were examined for their antibiotic susceptibility and biofilm formation. The <i>lux</i> reporter strains were constructed to assay the responses of <i>S. mutans</i> 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.<b>Results.</b> <i>S. mutans</i> 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 <i>S. mutans</i> to these peptide antibiotics involved the transcriptional activation of the <i>bceABRS</i> 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.<b>Conclusion.</b> The BceABRS four-component system in <i>S. mutans</i> is involved in sensing, response and resistance to host defence peptides, and is required for the biofilm formation and fitness of <i>S. mutans</i>.
Study Information
pubmed
2018
2018-06-01T00:00:00.000Z
10.1099/jmm.0.000733
11
29