Exclusion of catabolic regulation B (cbrB) gene in Pseudomonas aeruginosa attenuates the virulence at different glucose concentrations

Pseudomonas aeruginosa is a major opportunistic human pathogen that causes serious illnesses in people with compromised defenses. Given the heightened vulnerability of diabetic patients to such infections, this study investigates glucose as a signalling molecule in modulating the pathogen's virulence. In this study, in-frame deletions of the cbrB gene were carried out in P. aeruginosa strains PAO1 and a clinical isolate, ADW44, isolated from a diabetic patient, to elucidate the impact of glucose on virulence regulation. The results demonstrated that the cbrBmutants exhibited markedly reduced production of key virulence factors, including pyocyanin, siderophores, and alkaline protease, across all tested glucose concentrations. Elastase B activity and biofilm formation were also significantly diminished in the mutants. Quantitative real-time PCR analysis revealed significant downregulation of virulence and quorum sensing-related genes in the cbrB-deficient strains, in contrast to the glucose-induced upregulation observed in wild-type strains. In silico analyses further supported the indirect regulatory role of cbrB in QS gene networks. These findings suggest that the cbrB gene may play a crucial role in regulating the virulence of P. aeruginosa, particularly in the presence of external glucose, influencing multiple virulence factors and gene expressions critical for infection and pathogenicity in diabetic individuals.