Phenotypic and genotypic characterization of a hypervirulent carbapenem-resistant Klebsiella pneumoniae ST17-KL38 clinical isolate harboring the carbapenemase IMP-4

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is a threat to global public health. We characterized a sequence type 17 (ST17) K. pneumoniae clinical isolate that was resistant to carbapenems and belonged to serotype KL38/O2. Its complete genome is comprised of a 5.1-Mb chromosome and two conjugative plasmids. The 52,578-bp N-type plasmid pXH210-IMP contains the blaIMP-4 carbapenemase gene and the quinolone resistance gene qnrS1. The 272,742-bp FII(K)-9:FIB(K)-10 plasmid pXH210-AMV carries an array of genes that confer resistance to aminoglycosides, chloramphenicol, quinolones, tetracycline, sulfonamides, trimethoprim, arsenic, copper, and silver. However, the XH210 genome otherwise lacks the genes that are considered characteristic markers of hypervirulence in K. pneumoniae. The virulence potential of XH210 was assessed using a random forest algorithm predictive model, as well as Galleria mellonella and mouse infection models. The results of these were concordant and suggested that XH210 is hypervirulent and therefore a CR-hvKP strain. This worrying convergence of virulence and clinically significant antibiotic resistance is particularly concerning given the absence of typical hypervirulence markers. Further investigations are required to understand the virulence mechanisms of XH210 and to improve the diagnostics of hypervirulent K. pneumoniae. IMPORTANCE The combination of drug resistance and hypervirulence significantly limits the available treatment options for life-threatening infections caused by multidrug-resistant hvKP, especially CR-hvKP. To date, research on IMP-producing CR-hvKP is extremely scarce, and the virulence mechanisms of CR-hvKP are far more complicated and diverse than has been described in the literature so far. In this study, we characterized the tigecycline-resistant and IMP-4 carbapenemase-producing ST17 K. pneumoniae isolate XH210 from a human blood sample. Importantly, XH210 exhibits hypervirulence but does not possess traits that are frequently associated with the phenotype, highlighting the urgent need to improve identification of potentially hypervirulent isolates and enhance active surveillance of CR-hvKP strains to prevent their dissemination.