Carbon catabolite repression (CCR) in Gram‑positive bacteria is a sophisticated, evolutionarily tuned regulatory network that integrates carbon availability with global cellular physiology. This review traces the development from initial observations of CCR to the molecular elucidation of catabolite control protein A (CcpA)-mediated control, describing the roles of HPr, Crh, and HPrK/P in sensing glycolytic flux and transcriptional regulation. CCR ensures the preferential utilisation of the most efficient carbon source while simultaneously suppressing unnecessary catabolic pathways, thereby regulating a wide range of biological processes. Species‑specific variations in CCR underscore the ecological and evolutionary diversity of this system. Besides metabolism, CCR influences pathogenicity in some pathogenic bacteria, linking nutrient sensing to host interaction strategies. Its multidimensional impacts extend to biotechnology, fermentation optimisation, probiotic performance, and potential antimicrobial strategies targeting nutrient prioritisation. As omics‑based approaches reveal CCR as a global integrator of carbon, nitrogen, and stress pathways, future research must unravel species‑specific architectures, regulatory nuances, and evolutionary implications to understand and harness the complex regulatory system. • CCR integrates carbon availability with global physiology in Gram‑positive bacteria. • CcpA–HPr/Crh complexes link glycolytic flux to transcriptional regulation. • Preferred substrates vary by species, revealing diverse CCR hierarchies. • CCR influences stress responses, sporulation, virulence, and fermentation. • Atypical systems like Geobacillus kaustophilus challenge glucose‑centric CCR models.
Ken-ichi Yoshida (Wed,) studied this question.