Cell density- and ComE-dependent expression of a group of mutacin and mutacin-like genes in Streptococcus mutans

Abstract

Streptococcus mutans is a major cariogenic inhabitant of the high cell density oral biofilm (dental plaque). In previous studies, we showed that production of one of its virulence factors, the bacteriocin mutacin IV, was regulated by high cell density as well as the competence regulatory system ComED. In this study, we utilized luciferase fusions and real-time reverse transcriptase polymerase chain reaction (RT-PCR), to demonstrate that high cell density and ComED also regulate an uncharacterized group of mutacin and mutacin-like genes. Under high cell density or in the presence of externally added competence-stimulating peptide (CSP), gene expression increased 10- to 30-fold. Interestingly, high cell density was able to bypass the requirement for CSP addition. However, both cell density and CSP-dependent gene expression had a strict requirement for the ComE response regulator.

Streptococcal Antagonism in Oral Biofilms:Streptococcus sanguinisandStreptococcus gordoniiInterference withStreptococcus mutans

“…Furthermore, S. pneumoniae controls the expression of the competence operon comCDE in an oxygendependent process via the two-component signal transduction system CiaRH (10). The expression of the competence genes in S. mutans is coordinated with the expression of a group of bacteriocins and bacteriocin-like genes (19); accordingly, the expression of the bacteriocin mutacin IV was elevated under aerobic conditions in our studies. During the preparation of the present study, Ahn et al (3) reported the oxygen-dependent upregulation of the mutacin IV gene and the competence system for S. mutans using DNA microarrays, further supporting our results.…”

“…5). The expression of nlmA is controlled by the ComDE two-component system in response to the competence-stimulating peptide CSP (17,19). To learn whether oxygen-dependent regulation of nlmA is controlled by ComDE, the expression of comC and comE was measured in aerobic and anaerobic cultures.…”

“…For example, S. mutans shows cell density-dependent expression of bacteriocins mutacin I and mutacin IV when inoculated before S. sanguinis in an in vitro plate assay. Conversely, S. sanguinis produces H 2 O 2 when inoculated before S. mutans (19). These compounds are able to inhibit the competing species to keep their numbers low.…”

StreptococcusAdherence and Colonization

“…Thus, by expressing bacteriocins when cell numbers are high, bacteria are able to kill competing species when nutrients become limited. Such a strategy has been seen for S. mutans expression of the lantibiotic mutacin I, which acts against most gram-positive bacteria, and the nonlantibiotic mutacin IV, which targets predominantly mitis group streptococci and is associated with the LuxS/ HdrRM and ComED regulatory systems, respectively (318,402,404). Interestingly, the coordination of mutacin IV and competence development has been proposed to be a mechanism for S. mutans to acquire DNA from bacteriocin-sensitive streptococci, thereby promoting genetic diversity (317).…”

Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks

“…Recent studies had revealed the bifunctional nature of the ComED system showing a dual response as an activator of nlmC and repressor of comC. The researchers also reveal the puzzle behind the dual opposing characteristics of ComED as nlmC share an intergenic region (IGSA499) with the divergently transcribed comC [47,48]. Further, experiments show that the nlmC expression in comD mutant show [40-fold fold and [fourfold reduction in comparison with the wild-type under CSP-induced or un-induced state respectively [49].…”