(Competence) Operon Is Regulated by CcpA in Streptococcus pneumoniae D39.

Natural transformation plays an important role in the formation of drug-resistant bacteria. Exploring the regulatory mechanism of natural transformation can aid the discovery of new antibacterial targets and reduce the emergence of drug-resistant bacteria. Competence is a prerequisite of natural transformation in Streptococcus pneumoniae, in which operon is the core regulator of competence. To date, only ComE has been shown to directly regulate transcription. In this study, a transcriptional regulator, the catabolite control protein A (CcpA), was identified that directly regulated transcription. We confirmed that CcpA binds to the -acting catabolite response elements (cre) in the promoter region to regulate transcription and transformation. Moreover, CcpA can coregulate transcription with phosphorylated and dephosphorylated ComE. Regulation of transcription and transformation by CcpA was also affected by carbon source signals. Together, these insights demonstrate the versatility of CcpA and provide a theoretical basis for reducing the emergence of drug-resistant bacteria. Streptococcus pneumoniae is a major cause of bacterial infections in humans, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis. Like most streptococci, S. pneumoniae is naturally competent and employs this ability to augment its adaptive evolution. The current study illustrates CcpA, a carbon catabolite regulator, can participate in the competence process by regulating transcription, and this process is regulated by different carbon source signals. These hidden abilities are likely critical for adaptation and colonization in the environment.