Dataset Information

Phenotypic and Genotypic Characterization of a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae ST17-KL38 Clinical Isolate Harboring the Carbapenemase IMP-4.

ABSTRACT: 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 bla_IMP-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.

SUBMITTER: He J

PROVIDER: S-EPMC9045192 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a significant public health challenge worldwide, but research on IMP-producing CR-hvKP and its tigecycline resistance is extremely scarce. We report herein the recovery of two IMP-4-producing, capsular serotype K2, sequence type 65 (K2-ST65), hypervirulent K. pneumoniae isolates (C1672 and C2051), which caused severe and fatal infections in ICU patients, after retrospectively screening 3,285 carbapenem-resistant K. pneumoniae isolates from 26 provinces in China. Notably, C2051 also demonstrated tigecycline nonsusceptibility, mediated by a frameshift mutation in the TetR/AcrR family transcriptional regulator. Both strains harbored blaIMP-4 and critical plasmid-borne virulence genes (rmpA/rmpA2, iucA, and iroN) and demonstrated high virulence in Galleria mellonella, indicating CR-hvKP. The blaIMP-4 gene was located on the IncU- and IncN-type plasmids, which showed high stability in C1672 and C2051 after serial passage for 5 days, with retention rates of 87% and 93.7%, respectively. No significant differences in growth rates were observed among the parental strains and the corresponding resistance plasmid-cured mutants (P = 0.5273), suggesting that strains carrying the blaIMP and virulence plasmids have the potential to exist for a long time without compromising fitness. The genetic environments of the blaIMP-4 gene in both strains were similar, and it has been inferred that the genetic regions of blaIMP-4 were inserted into different backbones. Several conjugal transfer genes, such as traO, traE, traN, and traBCD, were identified in the blaIMP-4-bearing plasmid of C2051, suggesting a higher ability for plasmid transmission. The convergence of IMP carbapenemase and tigecycline nonsusceptibility in a classic hypervirulent K. pneumoniae lineage highlights the need to enhance clinical awareness and epidemiologic surveillance. IMPORTANCE To date, research on IMP-producing CR-hvKP is extremely scarce. Only one case of urinary tract infection caused by an IMP-6-producing K1-ST23 hypervirulent K. pneumoniae isolate in Japan was recorded, with a limited description of clinical information and genomic features. None of the published studies examined the virulence of the reported strains or the stability and fitness of resistance plasmids or presented a phylogenetic analysis. This dearth of data is notable because CR-hvKP infections are increasingly identified, but critical characteristics of the emerging resistance mediated by IMP carbapenemases in CR-hvKP remain unknown. Here, we report the emergence of two IMP-4 carbapenemase-producing K2-ST65 hypervirulent K. pneumoniae isolates that caused severe and fatal infections in clinical settings in China. Notably, one of them also demonstrated tigecycline nonsusceptibility. These strains carrying blaIMP and virulence plasmids had the potential to exist for a long time without compromising their fitness, highlighting the urgent need to enhance clinical awareness and epidemiologic surveillance to prevent their dissemination.

Project description:BackgroundThe convergence of hypervirulence and carbapenem resistance in the bacterial pathogen Klebsiella pneumoniae represents a critical global health concern. Hypervirulent K. pneumoniae (hvKp) strains, frequently from sequence type 23 (ST23) and having a K1 capsule, have been associated with severe community-acquired invasive infections. Although hvKp were initially restricted to Southeast Asia and primarily antibiotic-sensitive, carbapenem-resistant hvKp infections are reported worldwide. Here, within the carbapenemase production Enterobacterales surveillance system headed by the Chilean Public Health Institute, we describe the isolation in Chile of a high-risk ST23 dual-carbapenemase-producing hvKp strain, which carbapenemase genes are encoded in a single conjugative plasmid.ResultsPhenotypic and molecular tests of this strain revealed an extensive resistance to at least 15 antibiotic classes and the production of KPC-2 and VIM-1 carbapenemases. Unexpectedly, this isolate lacked hypermucoviscosity, challenging this commonly used hvKp identification criteria. Complete genome sequencing and analysis confirmed the K1 capsular type, the KpVP-1 virulence plasmid, and the GIE492 and ICEKp10 genomic islands carrying virulence factors strongly associated with hvKp. Although this isolate belonged to the globally disseminated hvKp clonal group CG23-I, it is unique, as it formed a clade apart from a previously reported Chilean ST23 hvKp isolate and acquired an IncN KPC-2 plasmid highly disseminated in South America (absent in other hvKp genomes), but now including a class-I integron carrying blaVIM-1 and other resistance genes. Notably, this isolate was able to conjugate the double carbapenemase plasmid to an E. coli recipient, conferring resistance to 1st -5th generation cephalosporins (including combinations with beta-lactamase inhibitors), penicillins, monobactams, and carbapenems.ConclusionsWe reported the isolation in Chile of high-risk carbapenem-resistant hvKp carrying a highly transmissible conjugative plasmid encoding KPC-2 and VIM-1 carbapenemases, conferring resistance to most beta-lactams. Furthermore, the lack of hypermucoviscosity argues against this trait as a reliable hvKp marker. These findings highlight the rapid evolution towards multi-drug resistance of hvKp in Chile and globally, as well as the importance of conjugative plasmids and other mobile genetic elements in this convergence. In this regard, genomic approaches provide valuable support to monitor and obtain essential information on these priority pathogens and mobile elements.

Dataset Information

Phenotypic and Genotypic Characterization of a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae ST17-KL38 Clinical Isolate Harboring the Carbapenemase IMP-4.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets