DksA enhances hypervirulent Klebsiella pneumoniae intestinal colonization by remodeling RNA polymerase to promote carbon source utilization

In this study, we employed transposon insertion sequencing (Tn-seq) to systematically identify metabolic genes associated with intestinal colonization in hypervirulent Klebsiella pneumoniae (hvKp).

By integrating high-throughput screening with in vivo phenotypic validation, we identified the global transcriptional regulator DksA as a key factor that markedly enhances hvKp intestinal colonization. Mechanistically, DksA appears to promote colonization by enhancing carbon source metabolism. Combined transcriptomic analyses with homology modeling and molecular dynamics simulations further revealed that DksA induces cascade allosteric remodeling of key RNA polymerase structural domains, thereby enhancing hvKp utilization of common intestinal carbon sources and facilitating intestinal colonization.