LiaS Regulates Virulence Factor Expression in Streptococcus mutans

Streptococcus mutans, a major oral pathogen responsible for dental caries formation, possesses a variety of mechanisms for survival in the human oral cavity, where the conditions of the external environment are diverse and in a constant state of flux. The formation of biofilms, survival under conditions of acidic pH, and production of mutacins are considered to be important virulence determinants displayed by this organism. Biofilm formation is facilitated by the production of GbpC, an important cell surface-associated protein that binds to glucan, an adhesive polysaccharide produced by the organism itself. To better understand the nature of the environmental cues that induce GbpC production, we examined the roles of 14 sensor kinases in the expression of gbpC in S. mutans strain UA159. We found that only the LiaS sensor kinase regulates gbpC expression, while the other sensor kinases had little or no effect on gbpC expression. We also found that while LiaS negatively regulates gbpC expression, the inactivation of its cognate response regulator, LiaR, does not appear to affect the expression of gbpC. Since both gbpC expression and mutacin IV production are regulated by a common regulatory network, we also tested the effect of the liaS mutation on mutacin production and found that LiaS positively regulates mutacin IV production. Furthermore, reverse transcription-PCR analysis suggests that LiaS does so by regulating the expression of nlmA, which encodes a peptide component of mutacin IV, and nlmT, which encodes an ABC transporter. As with the expression of gbpC, LiaR did not have any apparent effect on mutacin IV production. Based on the results of our study, we speculate that LiaS is engaged in cross talk with one or more response regulators belonging to the same family as LiaR, enabling LiaS to regulate the expression of several genes coding for virulence factors.