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We characterized the role of catabolite control protein A (ccpA) in the physiology and virulence of Streptococcus pneumoniae. S. pneumoniae has a large percentage of its genome devoted to sugar uptake and metabolism, and therefore, regulation of these processes is likely to be crucial for fitness in the nasopharynx and may play a role during invasive disease. In many bacteria, carbon catabolite repression (CCR) is central to such regulation, influencing hierarchical sugar utilization and growth rates. CcpA is the major transcriptional regulator in CCR in several gram-positive bacteria. We show that CcpA functions in CCR of lactose-inducible β-galactosidase activity in S. pneumoniae. CCR of maltose-inducible α-glucosidase, raffinose-inducible α-galactosidase, and cellobiose-inducible β-glucosidase is unaffected in the ccpA strain, suggesting that other regulators, possibly redundant with CcpA, control these …