Genomic Epidemiology of Carbapenemase-Producing Klebsiella Pneumoniae in China

Abstract

The rapid spread of carbapenemase-producing Klebsiella pneumoniae (cpKP) poses serious threats to public health; however, the underlying genetic basis for its dissemination is still unknown. We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing. The results showed that most cpKP isolates were categorized into clonal group 258 (CG258), in which ST11 was the dominant clone. Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates. Additionally, carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates, and most blaKPC genes were located in five major incompatibility (Inc) groups of blaKPC-harboring plasmids. Importantly, three advantageous combinations of host–blaKPC-carrying plasmid (Clade 3.1+3.2–IncFIIpHN7A8, Clade 3.1+3.2–IncFIIpHN7A8:IncR, and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC) were identified to confer cpKP isolates the advantages in both genotypes (strong correlation/coevolution) and phenotypes (resistance/growth/competition) to facilitate the nationwide spread of ST11/CG258 cpKP. Intriguingly, Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008. We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections. Thus, the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China, and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.

Genomic Analysis of KPC-2-Producing Klebsiella pneumoniae ST11 Isolates at the Respiratory Department of a Tertiary Care Hospital in Beijing, China

“…They are usually large (>100 kb), but with low copy numbers and often carry an additional replicon type to initiate replication ( Ogbolu et al, 2013 ). In this study, dual replicons such as IncFII pHN7A8 replicon/IncR and IncFII pHN7A8 /Inc pA1763–KPC had also been reported in other studies in China ( Feng et al, 2019 ; Li et al, 2022 ). Inc pA1763–KPC replicon often coexists with an auxiliary replicon with the major replicons (such as IncFII and IncR) to compose multireplicon plasmids, represented by plasmids p0716-KPC ( Feng et al, 2017 ).…”

Ceftazidime/Avibactam-Based Versus Polymyxin B-Based Therapeutic Regimens for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection in Critically Ill Patients: A Retrospective Cohort Study

“…According to the corresponding statistics from the China Antimicrobial Surveillance Network, rapidly increasing incidence and prevalence rates of CRKP infection have been observed from 2.9% in 2005 to 25% in 2021 [5]. K. pneumoniae carbapenemase (KPC) is the most clinically common carbapenemase in CRKP strains in China [6][7][8].…”

Distribution and Current State of Molecular Genetic Characterization in Pathogenic Free-Living Amoebae

“…On the other hand, genomic epidemiology is also applied to understand other types of diseases, mainly those caused by Escherichia coli [ 153 , 154 ], Shigella spp. [ 155 ], Klebsiella pneumoniae [ 156 ], Corynebacterium diphtheriae [ 157 ], Staphylococcus aureus [ 154 , 158 ], Enterococcus faecalis [ 154 ], and Mycobacterium tuberculosis [ 159 ]. Although this discipline is more developed in bacteria and now in viruses, we can find extensive reports on emerging fungal pathogens [ 160 , 161 , 162 , 163 , 164 ] describing antifungal resistance mechanisms or shared synteny among geographically diverse species.…”