Epidemiological Characteristics and Formation Mechanisms of Multidrug-Resistant Hypervirulent Klebsiella pneumoniae

Abstract

Multi-drug resistance (MDR) and hypervirulence (hv) were exhibited by different well-separated Klebsiella pneumoniae lineages in the past, but their convergence clones-MDR-hypervirulent K. pneumoniae (HvKPs)-both highly pathogenic and resistant to most available antibiotics, have increasingly been reported. In light of the clonal lineages and molecular characteristics of the studied MDR-HvKP strains found in the literature since 2014, this review discusses the epidemiology of MDR-HvKPs, in particular summarizing the three general aspects of plasmids-associated mechanisms underlying the formation of MDR-HvKPs clones: MDR-classic K. pneumoniae (cKPs) acquiring hv plasmids, hvKPs obtaining MDR plasmids, and the acquisition of hybrid plasmids harboring virulence and resistance determinants. A deeper understanding of epidemiological characteristics and possible formation mechanisms of MDR-HvKPs is greatly needed for the proper surveillance and management of this potential threat.

Keywords: Klebsiella pneumoniae; epidemiology; formation mechanism; horizontal gene transfer; hypervirulent; mobile genetic elements; multi-drug resistance; plasmid.

FIGURE 1

Model diagram of the possible evolution pathway of MDR-hvKPs mediated by a hybrid plasmid. ① MDR plasmids first transfer into hvKPs, then antimicrobial resistance genes are integrated or transposed into hv plasmid harbored by hvKPs, resulting in the formation of hybrid plasmids with most hv genes-bearing regions and the MDR-hvKPs of hv-associated STs (①-A). Alternatively, if the genes encoding the self-transfer conjugative system are integrated into the virulence plasmid, together with the resistance determinants, the hybrid plasmids will be conferred self-transmission and conjugativity transfer into any bacterial host including cKPs to become MDR-HvKPs (①-B). In addition, with the help of other conjugative plasmids this hybrid plasmid can be possibly transferred into other cKPs to form MDR-hvKPs of MDR- or cKP-linked STs (①-C). ② If the In, Tn, and (or) Is further carry hv genes from the hv plasmid into other resistance plasmids, hybrid plasmids with most sites of resistance plasmid characteristics are formed. They can be transferred into either hvKPs (①-②-A) or cKPs (①-②-B) to form MDR-hvKPs via their conjugal transfer system.