CcpA-dependent and-independent control of beta-galactosidase expression in streptococcus pneumoniae occurs via regulation of an upstream phosphotransferase system-encoding operon

A spontaneous mutant of Streptococcus pneumoniae strain D39 exhibiting elevated [beta]-galactosidase activity was identified. We determined that the [beta]-galactosidase activity was due to BgaA, a surface protein in S. pneumoniae, and that the expression of bgaA was regulated. Transcription analyses demonstrated expression of bgaA in the constitutive [beta]-galactosidase ([BgaA.sup.C]) mutant, but not in the parent. [beta]-Galactosidase expression was induced in the parent under specific growth conditions; however, the levels did not reach those of the [BgaA.sup.C] mutant. We localized the mutation resulting in the [BgaA.sup.C] phenotype to a region upstream of bgaA and in the promoter of a phosphoenolpyruvate-dependent phosphotransferase system (PTS) operon. The mutation was in a catabolite-responsive element (cre) and affected the binding of CcpA (catabolite control protein A), a key regulator of many carbon metabolism genes. The pts operon and bgaA were cotranscribed, and their transcription was regulated by CcpA. Deletion of ccpA altered [beta]-galactosidase activity, leading to a sevenfold increase in the parent but a fivefold decrease in the [BgaA.sup.C] mutant. The resulting [beta]-galactosidase activities were the same in the two strains, suggesting the presence of a second repressor. The presence of glucose in the growth medium resulted in pts-bgaA repression by both CcpA and the second repressor, with the latter being important in responding to the glucose concentration. Expression of [beta]-galactosidase is important for S. pneumoniae adherence during colonization of the nasopharynx, a site normally devoid of glucose. CcpA and environmental glucose concentrations thus appear to play important roles in the regulation of a niche-specific virulence factor.