Examination of the HdrRM Regulon Yields Insight into the Competence System of Streptococcus Mutans

Previous studies have identified the hdrRM operon as a novel regulatory system induced by conditions of high cell density. Little is known about the genes under the control of this system, but a variety of important phenotypes are associated with either hdrR overexpression or mutation of hdrM. To characterize the regulatory function of the HdrRM system in Streptococcus mutans we used a microarray approach to compare the transcriptional profiles of an hdrR overexpression strain with an hdrM mutant. Both strains exhibited almost identical profiles, which included all of the known late competence genes as well as a variety of competence-induced bacteriocins. Through a combination of real-time reverse transcription-polymerase chain reaction (PCR), reporter gene analysis and random amplification of complementary DNA ends PCR, we confirmed the role of comX as a central intermediate regulator of numerous genes in the hdrRM regulon. Through these studies, we also identified novel comX-regulated genes required for natural competence. Taken together, our results suggest that the primary function of the HdrRM system is to regulate the late competence genes together with various bacteriocins. This occurs independently of the ComCDE system, even though both systems regulate nearly identical genes. This suggests that S. mutans has multiple parallel input sensory systems that control the same output response: the induction of natural competence and concurrent production of bacteriocins.