PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 42688289

Coexistence of carbapenemase and hypervirulence-associated genes among Klebsiella pneumoniae high-risk clones in Hungary.

Lilla Buzgó·Csongor Freytag·Dániel Göbhardter·Levente Laczkó·László Miló·Leila Holub·Adrienn Hanczvikkel·Erika Ungvári·László Majoros·Katalin Kamotsay·Katalin Papp·Katalin Kristóf·Gábor Kardos·Ákos Tóth
View original source ↗Export metadata ↓

Abstract

INTRODUCTION: Strains of Klebsiella pneumoniae carrying hypervirulence and carbapenemase genes represent a rapidly emerging global public health threat. Our study aimed to comprehensively characterise the genomics of hypervirulence-associated and carbapenemase genes carrying K. pneumoniae (hv(a)CpKp) isolates in Hungary. MATERIALS AND METHODS: Between January 2022 and April 2024, 89 aerobactin (iucA-D/iutA)-positive non-duplicate carbapenemase-producing K. pneumoniae isolates from 15 Hungarian healthcare institutes underwent short-read (Illumina, MiSeq, NextSeq) whole-genome sequencing, followed by detailed plasmid analysis using long-read sequencing (Nanopore, MinION) in a representative subset of 32 strains. RESULTS: Most isolates (79/89) belonged to the high-risk clone ST147. Hypervirulence-associated (hva) genes-including rmpA/rmpA2, peg344, shiF, iucA-D, and iutA-were universally present, and 59 isolates possessed chromosomally integrated yersiniabactin loci. Most isolates (87/89) carried the bla NDM-1 carbapenemase gene. Hypervirulence-associated genes were most frequently (29/32) associated with IncHI1B/IncFIB(Mar) plasmids. Notably, we identified plasmids carrying both hva and carbapenemase genes-designated as hybrid plasmids-in 13 of 32 strains. The bla NDM-1 was linked to the IS26 transposase and was present in conserved, identical cassettes on all bla NDM-1-carrying plasmids. DISCUSSION/CONCLUSION: Our study identified hv(a)CpKp strains, particularly the ST147 clone, circulating in Hungary. Our findings highlight the need for routine virulence gene monitoring and continuous genomic and plasmid-based surveillance to mitigate the clinical and epidemiological impact of emerging hv(a)CpKp lineages.

Explore related subjects

Klebsiella pneumoniaeST147blaNDM-1 carbapenemasehybrid plasmidshypervirulence-associated genesplasmid analysiswhole-genome sequencingJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lilla Buzgó, Csongor Freytag, Dániel Göbhardter, Levente Laczkó, László Miló, Leila Holub, Adrienn Hanczvikkel, Erika Ungvári, László Majoros, Katalin Kamotsay, Katalin Papp, Katalin Kristóf, Gábor Kardos, Ákos Tóth. 2026-08-19. Coexistence of carbapenemase and hypervirulence-associated genes among Klebsiella pneumoniae high-risk clones in Hungary.. https://doi.org/10.3389/fmicb.2026.1870558

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Post-infection colonization and recurrent infections by ST11-KL64 carbapenem-resistant Klebsiella pneumoniae: a study of within-host evolution.

Bacteria pose a serious threat to hosts through adaptive mutations that confer stress resistance and promote persistent colonization. Here, we describe an adaptive evolution event involving eight highly similar ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, isolated from a non-infected inpatient who acquired two distinct CRKP strains, CRKP-F1 and CRKP-S2 during the first hospitalization, recovered, and was discharged after receiving antimicrobial therapy but subsequently experienced two additional recurrent febrile episodes and re-admission. The strain CRKP-S2 showed significantly enhanced resistance to oxidative stress, survival within macrophages, and internalization ability, and carried an additional ~72 kb fragment containing oxidative stress response factors (including NAD(P)-dependent oxidoreductases), and a ~ 19kb plasmid fragment harboring catA2, sul2, umuC/D genes, compared to the initial strain CRKP-F1. All four strains, CRKP-B3, CRKP-U4, CRKP-F5 and CRKP-S6, from the second hospitalization exhibited higher genetic similarity to CRKP-S2 than each other, and each of these strains has its own unique mutations compared to CRKP-S2. The third-hospitalization strain CRKP-U7 displayed the highest average nucleotide identity (ANI) with CRKP-S2, and possessed unique mutations in cecR, rlmA1, and selB, distinct from second-hospitalization strains. However, the last strain, CRKP-B8, carries a new gene mutation based on CRKP-U7 and exhibits greater host adaptability than all other isolates. While these findings are suggestive, whether the ~72-kb and ~19-kb fragments and mutations in CRKP-S2 drove enhanced colonization, and whether subsequent mutations contributed to subclones linked to recurrent febrile, or merely coincided, remains unclear. The possibility of mixed colonization by co-circulating subclones cannot be excluded, and functional validation is needed.

Klebsiella pneumoniae↗
PubMed2026

Comparative and Subtractive Genomics Analysis of Multidrug-Resistant Klebsiella pneumoniae Strains for Novel Target Identification and Drug Repurposing Strategies.

The rapid rise of multidrug-resistant (MDR) Klebsiella pneumoniae has created a major global health challenge due to the limited availability of conserved therapeutic targets effective across diverse resistant strains. In this study, an integrative computational target-discovery and drug-repurposing framework was applied to six clinically relevant K. pneumoniae strains. Comparative genomic analysis identified 3012 conserved genes, which were subsequently filtered to nine essential, non-host homologous proteins. Among these, three conserved cytoplasmic proteins (accD, cpxR, and mraZ) were prioritized for functional analysis, with acetyl-CoA carboxylase subunit beta (accD) emerging as the most promising therapeutic target based on sequence conservation, predicted essentiality, subcellular localization, and pathway association. Structural assessment supported the reliability of the predicted accD model, whereas consensus binding-site analysis identified key residues suitable for ligand interaction. Virtual screening of FDA-approved drugs followed by molecular docking identified several compounds with favorable binding profiles toward accD. Subsequent molecular dynamics simulations, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), hydrogen-bond occupancy, principal component analysis (PCA), and PCA-based free energy landscape (FEL) analyses, consistently identified tenapanor, micafungin, deferoxamine, and cobicistat as the most stable protein-ligand complexes, with tenapanor exhibiting the most favorable overall structural and thermodynamic stability profile. These findings identify accD as a promising therapeutic target in MDR K. pneumoniae and suggest several FDA-approved compounds as potential candidates for drug repurposing. Although experimental validation is needed to confirm their biological activity and therapeutic potential, this study demonstrates the potential of integrating comparative genomics with molecular dynamics analyses to support antimicrobial target identification and drug repurposing against MDR bacterial pathogens.

Klebsiella pneumoniae↗
PubMed2026

Genomic and phenotypic characterization of Klebsiella pneumoniae phage KP Ø1: a novel lytic Slopekvirus targeting uropathogenic multidrug-resistant Klebsiella pneumoniae.

The rise of multidrug-resistant (MDR) uropathogenic gram-negative bacteria (GNB) necessitates the development of alternative therapeutic strategies. This study aimed to isolate, phenotypically characterize, and perform whole-genome sequencing of the bacteriophage demonstrating the broadest host range against MDR uropathogens. Fifty MDR GNB isolates were screened for lytic phages. The most promising candidate, Klebsiella pneumoniae phage KP Ø1, was characterized using plaque assay, Transmission Electron Microscopy (TEM), and pH/thermal stability testing. Genomic characterization was performed via whole-genome sequencing (WGS), with functional annotation and lifestyle prediction using PhaBOX and PhageScope software. Klebsiella pneumoniae was the most prevalent MDR uropathogen. Klebsiella pneumoniae phage KP Ø1 exhibited a 50% host range and high lytic titer (10⁸ PFU/mL). TEM revealed an icosahedral head and short contractile tail. Genomic characterization by WGS revealed that Klebsiella pneumoniae phage KP Ø1 possesses a 174,591 bp double-stranded deoxyribonucleic acid (dsDNA) genome containing 274 predicted open reading frames (ORFs). No lysogeny-related genes, toxins, or antibiotic resistance markers were detected, confirming its strictly lytic nature and supporting its potential as a candidate for phage therapy applications. The phage remained stable (10⁸ PFU/mL) across temperatures of - 20 °C to 50 °C; supporting its suitability for long-term biobanking and suggesting potential activity at physiological temperature, and across a pH range of 7-9. Klebsiella pneumoniae phage KP Ø1 is a novel, obligately lytic Slopekvirus whose genomic architecture, stability profile, and absence of lysogeny-associated, virulence, and antimicrobial resistance genes ( AMR) collectively support its candidacy for further preclinical evaluation as a phage therapy agent against uropathogenic MDR Klebsiella pneumoniae.

Klebsiella pneumoniae↗