Bacteria have evolved a set of regulatory pathways to adapt to the dynamic nutritional environment during the course of infection. However, the underlying mechanism of the regulatory effects by nutritional cues on bacterial pathogenesis is unclear. In the present study, we showed that the Pseudomonas aeruginosa catabolite repression control protein regulates the Pseudomonas quinolone signal quorum sensing, which further controls synthesis of virulence factor pyocyanin, biofilm formation and survival during infection models. Our study suggests that deregulation of the catabolite repression by P. aeruginosa might enhance its fitness during cystic fibrosis infections.