Regulation and Consequence of Serine Catabolism in Streptococcus pyogenes

The Gram-positive bacterium Streptococcus pyogenes (Group A Streptococcus, GAS), is found strictly in humans and is capable of causing a wide variety of infections. Here we demonstrate that serine catabolism in GAS is controlled by the transcriptional regulator, Spy49_0126c. We have designated this regulator SerR (serine catabolism regulator). Microarray and transcriptional reporter data show that SerR acts as a transcriptional repressor of multiple operons, including sloR and sdhBA. Purified recombinant SerR binds to promoters of both sloR and sdhB, demonstrating that this regulation is direct. Deletion of serR results in reduced culture yield of the mutant compared to wild-type when grown in defined medium unless additional serine is provided, suggesting that regulation of serine metabolism is 10 important for maximizing bacterial growth. Deletion of sloR or sdhB in the DserR mutant background restores growth to wild-type levels, suggesting that both operons have roles in serine catabolism. While reports have linked sloR function to streptolysin O expression, transport experiments with radiolabeled L-serine reveal that the sloR operon is required for rapid acquisition of serine, implicating a novel role for this operon in amino acid metabolism.