Capture of mobile genetic elements following intercellular conjugation promotes the production of ST11-KL64 CR-hvKP.

Abstract

Sequence type (ST)11 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) can cause life-threatening infections and is therefore of global concern. Despite its importance, the evolutionary history and mechanism for the emergence of ST11 CR-hvKP are unclear. In recent years, the detection rate of ST11 CR-hvKP has increased in a teaching hospital. Based on its clonal transmission, a conjugation experiment was performed between a hvKP strain AP8555 and a ST11 CRKP strain, resulting in two ST11 CR-hvKP strains. Research had confirmed that the virulence plasmid pAP855 was horizontally transferred to the CRKP strain to form the conjugant S270-Tc, which was recombined by mobile genetic elements to evolve into the conjugant S270-Tc-R. The S270-Tc-R had high virulence, high plasmid stability, and greater adaptability. Interestingly, it had high homology to clinically prevalent ST11 CR-hvKP strains using pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). This is the first demonstration that plasmid recombination in vitro has led to the formation of ST11 CR-hvKP strains. The clinical setting is a multi-factorial and multi-selection pressure environment that may stimulate the evolution of conjugant strains in the transition period to local strains in the stable period, and surveillance is urgently needed for infection control.

Importance: The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) heralded the onset of a new and rapidly worsening public health disaster on a global scale. More attention has been paid to its evolutionary history and mechanism, which currently remains unclear. In this study, a conjugation experiment was performed between a hvKP strain AP8555 and a ST11 CRKP strain, resulting in two ST11 CR-hvKP strains. We had confirmed that the virulence plasmid pAP855 was horizontally transferred to the CRKP strain to form the conjugant S270-Tc, which was recombined by mobile genetic elements to evolve into the conjugant S270-Tc-R. The S270-Tc-R had high virulence, high plasmid stability, and greater adaptability. Interestingly, it had high homology to clinically prevalent ST11 CR-hvKP strains using pulsed-field gel electrophoresis and whole-genome sequencing.