ArticlePLoS pathogens2022
Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- KPC-producing Klebsiella pneumoniae in Switzerland from 2024 to 2025: comparative genomics and cefiderocol resistance mechanisms analyses.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- In silico genomic analysis of resistome, virulome, and mobilome of β-lactamase-producing Klebsiella pneumoniae.Scientific reports · 2026Article
- OmpK36 GD insertion induces RpoS-dependentAntimicrobial agents and chemotherapy · 2026Article
- Chemical Characterization and Evaluation of Antimicrobial, Antioxidant, and Synergistic Activities ofPharmaceutics · 2026Article
- Novel Insights into Carbapenem Resistance: Mechanisms, Diagnostics, and Future Directions.Antibiotics (Basel, Switzerland) · 2026Review
- Activity of cefepime/enmetazobactam against highly multidrug-resistant bacterial isolates recovered from war-associated wounds in Ukraine.JAC-antimicrobial resistance · 2026Article
- Molecular Insights into Carbapenem Resistance inInternational journal of molecular sciences · 2026Review
- Genomic analysis reveals multi-level resistance network linking oxidative stress pathway mutations to cefiderocol resistance and clonal evolution inFrontiers in cellular and infection microbiology · 2026Article
- Harnessing interpretable deep learning to predict resistance inFrontiers in cellular and infection microbiology · 2026Article
- Comprehensive genomic characterization of multidrug-resistantFrontiers in microbiology · 2026Article
- Genomic characterization of ceftazidime/avibactam-resistant KPC-producingFrontiers in microbiology · 2026Article
- First identification of an ST11-KL64 hypervirulentFrontiers in microbiology · 2026Article
- Emergence and hospital dissemination of hypervirulent carbapenem-resistant Klebsiella pneumoniae lineages in eastern China.BMC microbiology · 2025Article
- Scarless excision of an insertion sequence in the OmpK36 promoter restores meropenem susceptibility in a non-carbapenemase-producingEmerging microbes & infections · 2025Article
- Article
- Identifying drivers of β-lactam/β-lactamase inhibitor resistance emergence and spread before their clinical deployment.medRxiv : the preprint server for health sciences · 2025Article
- Mechanisms of Cefiderocol Resistance in Carbapenemase-Producing Enterobacterales: Insights from Comparative Genomics.Antibiotics (Basel, Switzerland) · 2025Article
- Emergence of KPC-8-producingAntimicrobial agents and chemotherapy · 2025Article
- Evaluation of ceftazidime/avibactam in combination with colistin against KPC-2-producingJAC-antimicrobial resistance · 2025Article
- Mechanisms, therapeutic strategies, and emerging therapeutic alternatives for carbapenem resistance in Gram-negative bacteria.Archives of microbiology · 2025Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in outer membrane porins act in synergy with carbapenemase enzymes to increase carbapenem resistance in the important nosocomial pathogen, Klebsiella pneumoniae (KP). A key example is a di-amino acid insertion, Glycine-Aspartate (GD), in the extracellular loop 3 (L3) region of OmpK36 which constricts the pore and restricts entry of carbapenems into the bacterial cell. Here we combined genomic and experimental approaches to characterise the diversity, spread and impact of different L3 insertion types in OmpK36. We identified L3 insertions in 3588 (24.1%) of 14,888 KP genomes with an intact ompK36 gene from a global collection. GD insertions were most common, with a high concentration in the ST258/512 clone that has spread widely in Europe and the Americas. Aspartate (D) and Threonine-Aspartate (TD) insertions were prevalent in genomes from Asia, due in part to acquisitions by KP sequence types ST16 and ST231 and subsequent clonal expansions. By solving the crystal structures of novel OmpK36 variants, we found that the TD insertion causes a pore constriction of 41%, significantly greater than that achieved by GD (10%) or D (8%), resulting in the highest levels of resistance to selected antibiotics. We show that in the absence of antibiotics KP mutants harbouring these L3 insertions exhibit both an in vitro and in vivo competitive disadvantage relative to the isogenic parental strain expressing wild type OmpK36. We propose that this explains the reversion of GD and TD insertions observed at low frequency among KP genomes. Finally, we demonstrate that strains expressing L3 insertions remain susceptible to drugs targeting carbapenemase-producing KP, including novel beta lactam-beta lactamase inhibitor combinations. This study provides a contemporary global view of OmpK36-mediated resistance mechanisms in KP, integrating surveillance and experimental data to guide treatment and drug development strategies.
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