Global evolution and geographic diversity of hypervirulent carbapenem-resistant Klebsiella pneumoniae

Abstract

In a large-scale, prospective, intercontinental study, Minggui Wang and colleagues1Wang M Earley M Chen L et al.Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study.Lancet Infect Dis. 2022; 22: 401-412Summary Full Text Full Text PDF PubMed Scopus (12) Google Scholar used whole-genome sequencing (WGS) and clinical investigations to show regional differences in the epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP). From 71 hospitals in eight countries, 991 strains of CRKP were collected to establish their clinical, epidemiological, and genomic characteristics. The authors noted regional differences between bacterial characteristics of CRKP populations and their associated patient cohorts. To supplement their work, we retrieved the genome sequences of 21 016 strains of CRKP from the National Center for Biotechnology Information GenBank database, including 697 complete genome sequences and 20 319 draft genome sequences, from 1980 to 2022 in 105 countries. The genomic characteristics of CRKP were investigated, including clonal lineages, carbapenemase genes, virulence genes, and capsule and lipopolysaccharide types (appendix pp 1–4). We found that carriage of genes specific to hypervirulent K pneumoniae was prevalent among CRKP strains (0·40–27·03%). Worldwide, 51·68% of CRKP strains have yersiniabactin genes, which are the virulence genes with the highest frequency. The proportion of CRKP harbouring yersiniabactin and aerobactin genes has increased significantly over the past two decades, with yersiniabactin genes increasing from 24·58% to 49·89% and aerobactin genes from 0·50% to 31·43%. Aerobactin genes (25·78%) were found mostly in CRKP strains in Asia. In the USA (16·05%) and South America (21·67%) the proportion of CRKP strains with the colibactin gene was much higher than in Asia (1·53%), Europe (0·71%), Africa (0·00%), Oceania (0·17%), and other north American countries (1·01%). Furthermore, we found that CRKP strains in China had a higher number of aerobactin, rmpADC, rmpA2, and yersiniabactin genes than did strains in other nations. The high prevalence of sequence type (ST) 11 CRKP with rmpA2 genes (28·94%) and of ST11 CRKP (36·29%) indicate the large proportion of hypervirulent K pneumoniae associated with dominant CRKP clones in China.2Gu D Dong N Zheng Z et al.A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study.Lancet Infect Dis. 2018; 18: 37-46Summary Full Text Full Text PDF PubMed Scopus (401) Google Scholar, 3Alcántar-Curiel MD Girón JA Klebsiella pneumoniae and the pyogenic liver abscess: implications and association of the presence of rpmA genes and expression of hypermucoviscosity.Virulence. 2015; 6: 407-409Crossref PubMed Scopus (18) Google Scholar These data show that the classic isolates of CRKP have already evolved into hypervirulent isolates and that a considerable proportion of CRKP strains should now be designated as hypervirulent CRKP. Highly pathogenic hypervirulent CRKP has been spreading rapidly worldwide, and requires increased clinical attention (figure). Accordingly, we developed the Bacterial Whole Genome Sequence Typing Database (BacWGSTdb), a freely accessible public repository for bacterial WGS typing and source tracking, to provide a one-stop solution to detecting highly pathogenic clones during their early stages of expansion.4Feng Y Zou S Chen H Yu Y Ruan Z BacWGSTdb 2·0: a one-stop repository for bacterial whole-genome sequence typing and source tracking.Nucleic Acids Res. 2021; 49: D644-D650Crossref Scopus (51) Google Scholar To prevent future transmission, real-time surveillance powered by WGS and stringent infection-control measures should be implemented. Rapid and cost-effective WGS is crucial for diagnosing and monitoring the outbreaks and transmission dynamics of bacterial infections.5Didelot X Bowden R Wilson DJ Peto TEA Crook DW Transforming clinical microbiology with bacterial genome sequencing.Nat Rev Genet. 2012; 13: 601-612Crossref PubMed Scopus (487) Google Scholar The genomic features and antimicrobial resistance of bacterial pathogens in low-income and middle-income countries might be underestimated due to the paucity of genomic data. Overall, our data highlight the global evolution and geographical variations of hypervirulent CRKP, advocate for active WGS-based surveillance of CRKP, and emphasise the pressing need for further prospective, multicentre, intercontinental studies. These efforts would aid in the development of appropriate infection-control measures to prevent further transmission of hypervirulent CRKP. We declare no competing interests. This work was supported by the National Natural Science Foundation of China (82102436, 82172314, 81401698) and the Zhejiang Provincial Natural Science Foundation of China (LY21H190001, LQ22H200001). Download .pdf (.26 MB) Help with pdf files Supplementary appendix Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort studyGlobal CRKP epidemics have important regional differences in patients’ baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions. Full-Text PDF