Evolution of Virulence Plasmids and Their Role in Clinical Adaptation and Virulence Expression of ST11 Carbapenem-Resistant Klebsiella Pneumoniae

Project: Research

View graph of relations

Description

Recent evidence shows that Klebsiella pneumoniae, a major causative agent of hospital infections, has undergone a series of evolutionary changes in the past decade that result in emergence of a range of phenotypic variants of clinical significance. Certain types of K. pneumoniae were evolved to become hypervirulent K. pneumoniae (HvKP) in the 1980s, while some other types have emerged into carbapenem-resistant K. pneumonia (CRKP), with ST11 being the most dominant type in Asian countries. In 2017, however, our research team discovered a new type of hypervirulent and carbapenem-resistant K.pneumoniae (CR-HvKP) strains that caused almost 100% mortality in infected patients. This new type of superbug was found to evolve through acquisition of a pLVPK-like virulence plasmid by ST11 CRKP strains, allowing such strains to evolve into clinically prevalent, carbapenem resistant and hypervirulent organisms. This new type of superbug has since been reported in many parts of the world, with a particularly high prevalence in Asian countries. Our recent surveillance data further showed that the recovery rate of ST11 CRKP strains carrying the virulence plasmid increased dramatically in clinical settings in China, reaching 50% in some hospitals. However, the virulence plasmid in many of these strains were found to harbor mutations in the rmpA/rmpA2 genes and deletions in different parts of the plasmid. The ST11 CRKP strains carrying such mutated plasmids were also found to cause infections with varied mortality rate, indicating that some of the mutated pLVPK-like plasmids may not encode hypervirulence but are nevertheless highly transmissible. These findings prompt us to hypothesize that acquisition of the virulence plasmid by ST11 CRKP is followed by a series of evolution events that would enhance plasmid stability and transmission potential. Yet how these evolutionary changes in the virulence plasmid affects the physiology and phenotypes of the host strain is not known. It is therefore necessary to assess the clinical impact of virulence plasmid-mediated adaptation events of ST11 CRKP. This research proposal describes our plan to 1) investigate the long term impact of acquisition of the virulence plasmid on virulence expression and phenotypic changes in ST11 CRKP; and 2) delineate mutations in rmpA/rmpA2 and deletions in different parts of the virulence plasmid that are necessary for stable and long term co-existence of this plasmid in ST11 CRKP. Findings in the proposed work shall provide insights into the design of intervention strategies to control the further spread of these clinically important ST11 CR-HvKP strains. 

Detail(s)

Project number9043113
Grant typeGRF
StatusActive
Effective start/end date1/01/22 → …