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.

Virulence Factors in Hypervirulent Klebsiella pneumoniae

“…Genetic factors and geographic conditions are likely to be relative risk factors for this situation (Sellick and Russo, 2018). The geographical distribution of MDR-hvKP also showed similar pattern that they were mostly found in Asian countries, although global spread has been documented (Li et al, 2014;Tang et al, 2020). The genetic backgrounds of hvKP varied, among which clonal group (CG) 23 strains are the most predominant (Liao et al, 2014;Shi et al, 2018).…”

“…However, novel hvKp sequence types continue to emerge, indicated the ongoing evolution of hvKP (Shankar et al, 2018). MDR-hvKP strains mainly belonged to ST11, and carbapenemresistant K. pneumoniae (CR-KP) MDR-hvKp ST11 strains have been described in China (Gu et al, 2018;Tang et al, 2020). Both ST11 and ST258 belong the CG258 clone and ST11 is a single locus variant to ST258.…”

“…Except for intrinsic resistance to ampicillin, hvKp strains are commonly susceptible to a variety of antibiotics, including cephalosporins and carbapenems; however, multidrug-resistant and hypervirulent (MDR-hv) strains have recently emerged, primarily due to horizontal transfer of plasmid-mediated resistance or virulence (Liu C. et al, 2020;Tang et al, 2020). The spread of hvKP, including MDR-hvKP strains, poses a serious threat to the public health, and studies on hvKP virulence are therefore imperative to comprehend the underlying pathogenesis and provide a theoretical basis for the treatment and prevention of infection.…”

Genome-Based Analysis of Klebsiella spp. Isolates from Animals and Food Products in Germany, 2013–2017

“…In the last decades, K. pneumoniae has also been reported as a cause of community-acquired infections, including liver abscesses, endophthalmitis, and meningitis in otherwise healthy individuals [ 7 , 12 ]. These infections are often caused by hypervirulent isolates representing specific K. pneumoniae lineages, e.g., sequence types ST23 and ST66 [ 13 , 14 ]. Hypervirulent strains possess a distinct portfolio of virulence factors, mainly several siderophore genes, and express specific capsule types (e.g., K1 or K2) [ 4 , 15 ].…”

Finding Order in the Chaos: Outstanding Questions in Klebsiella pneumoniae Pathogenesis

“…The emergence and possible dissemination of K. pneumoniae isolates that possess both multidrug resistance and hypervirulence (MDR-hvKp) is a major concern. This concern is warranted, as there are already reported cases of MDR-hvKp from numerous countries, and these convergent events cause life-threatening infections that are difficult, if not impossible, to treat ( 49 ) ( Fig. 2 ).…”