Three paralogous LysR-type transcriptional regulators control sulfur amino acid supply in Streptococcus mutans

The genome of Streptococcus mutans encodes 4 LysR-type transcriptional regulators (LTTRs), three of which, MetR, CysR (cysteine synthesis regulator), and HomR (homocysteine synthesis regulator), are phylogenetically related. MetR was previously shown to control methionine metabolic gene expression. Functional analysis of CysR and HomR was carried out by phenotypical studies and transcriptional analysis. CysR is required to activate the transcription of cysK encoding the cysteine biosynthesis enzyme, tcyABC and gshT genes encoding cysteine and glutathione transporter systems, and homR. HomR activates the transcription of metBC encoding methionine biosynthesis enzymes, tcyDEFGH involved in cysteine transport, and still uncharacterized thiosulfate assimilation genes. Control of HomR by CysR provides evidence of a cascade regulation for sulfur amino acid metabolism in S. mutans. Two conserved motifs were found in the promoter regions of CysR and HomR target genes, suggesting their role in the regulator binding recognition site. Both CysR and HomR require O-acetylserine to activate transcription. A global sulfur amino acid supply gene regulatory pathway is proposed for S. mutans, including the cascade regulation consequent to transcriptional activation of HomR by CysR. Phylogenetic study of MetR, CysR, and HomR homologues and comparison of their potential regulatory patterns among the Streptococcaceae suggest their rapid evolution.