Multiple sugar: phosphotransferase system permeases participate in catabolite modification of gene expression in Streptococcus mutans

Abstract

Streptococcus mutans is particularly well adapted for high‐affinity, high‐capacity catabolism of multiple carbohydrate sources. S. mutansenzyme II (EII^Lev), a fructose/mannose permease encoded by the levDEFG genes, and fruA, which encodes a hydrolase that releases fructose from fructan polymers, are transcriptionally regulated by the LevQRST four‐component signal transduction system. Here, we demonstrate that: (i) levDEFGX are co‐transcribed and the levE/F intergenic region is required for optimal expression of levFGX; (ii) D‐mannose is a potent inducer of the levD and fruA operons; (iii) CcpA regulates levD expression in a carbohydrate‐specific manner; (iv) deletion of the genes for the fructose/mannose‐EII enzymes of S. mutans (manL, fruI and levD) enhances levD expression; (v) repression of the LevQRST regulon by EII enzymes depends on the presence of their substrates and requires LevR, but not LevQST; and (vi) CcpA inhibits expression of the manL and fruI genes to indirectly control the LevQRST regulon. Further, the manL, ccpA, fruI/fruCD and levD gene products differentially exert control over the cellobiose and lactose operons. Collectively, the results reveal the existence of a global regulatory network in S. mutans that governs the utilization of non‐preferred carbohydrates in response to the availability and source of multiple preferred carbohydrates.