The cyclic AMP receptor protein (CRP) is a highly conserved global transcriptional regulator that integrates carbon metabolism and environmental adaptation in bacteria. However, its systematic role in the regulation of virulence in K. pneumoniae remains poorly understood; In this study, we constructed a crp deletion mutant (Δcrp) and a complemented strain (c-Δcrp) and employed a combination of in vitro virulence assays, in vivo infection models, transcriptomic profiling, and functional metabolic analyses to dissect the CRP-mediated metabolism–virulence regulatory axis; We show that crp deficiency does not significantly alter susceptibility to clinically relevant antibiotics but markedly impairs biofilm formation, motility, and host cell adhesion and invasion. In murine infection models, the Δcrp strain exhibits significantly reduced pulmonary colonization and lethality. Transcriptomic analysis reveals broad downregulation of phosphotransferase system (PTS)-associated genes, including srlA/srlB/srlE, mtlA and malX. Functional assays further demonstrate that crp loss severely compromises growth on multiple host-relevant carbon sources and is accompanied by aberrant accumulation of intracellular ATP and NADH, indicative of disrupted metabolic homeostasis; Collectively, these findings identify crp as an important regulator associated with PTS-mediated carbon metabolic balance, and virulence-related phenotypes in K. pneumoniae. Accordingly, targeting the CRP–PTS axis may offer a theoretical basis for metabolism-oriented anti-virulence interventions against K. pneumoniae by attenuating pathogenicity.
Liu et al. (Tue,) studied this question.