The Global Regulator CodY in Streptococcus thermophilus Controls the Metabolic Network for Escalating Growth in the Milk Environment

Abstract

ABSTRACTCodY is a transcriptional regulator conserved in the low-GC group of Gram-positive bacteria. In this work, we demonstrated the presence inStreptococcus thermophilusST2017 of a functional member of the CodY family of global regulatory proteins,S. thermophilusCodY (CodYSt). The CodYStregulon was identified by transcriptome analysis; it consisted predominantly of genes involved in amino acid metabolism but also included genes involved in several other cellular processes, including carbon metabolism, nutrient transport, and stress response. It was revealed that CodYStrepressed the transformation of the central metabolic pathway to amino acid metabolism and improved lactose utilization. Furthermore, the glutamate dehydrogenase gene (gdhA), repressed by CodYSt, was suggested to coordinate the interconversion between carbon metabolism and amino acid metabolism and to play an important role on the optimal growth ofS. thermophilusST2017 in milk. A conserved CodYStbox [AA(T/A)(A/T)TTCTGA(A/C)AATT] was indeed required forin vitrobinding of CodYStto the target regions of DNA. These results provided evidence for the function of CodYSt, by which this strain coordinately regulates its various metabolic pathways so as to adapt to the milk environment.