CpxR promotes the carbapenem antibiotic resistance of Klebsiella pneumoniae by directly regulating the expression and the dissemination of bla KPC on the IncFII conjugative plasmid.

is an important human pathogen known for its resistance to carbapenem antibiotics, especially the increasing carbapenem-resistant hypervirulent variants. The carbapenem resistance is mainly caused by the carbapenemase gene which was commonly found on the IncFII transferable plasmids in ST11 isolates in regions of China. However, the mechanisms of the plasmid-carrying regulation by the host strain are not clear. To investigate the chromosome-encoded two-component system (TCS) that regulates the carbapenem resistance of caused by , twenty-four TCSs of a carbapenem-resistant classical ST11 clinical isolate were knocked out. The deletion mutation of the TCS regulator exhibited increased sensitivity to carbapenem, which could be restored by complementation with . Electrophoretic mobility shift, isothermal titration calorimetry and DNase I footprinting results revealed that CpxR directly bound to the promoter DNA of and the binding was abolished by disrupting the DNA-binding domain in CpxR. The subsequent assays using the reporter system and qPCR showed that CpxR upregulates the transcription of . Notably, CpxR was also found to activate the transfer of the -carrying IncFII plasmid between the hypervirulent and isolates, in which CpxR promoted the transcription of the operon via binding to its promoter region. These results provide an important insight into the regulation of the host factor CpxR in the plasmid-carrying carbapenemase gene in the classical and hypervirulent .