Work

Molecular and metabolic features of colistin-resistant ST11 carbapenem-resistant Klebsiella pneumoniae

Year: 2026

Type: article

Abstract: Introduction. The emergence of colistin-resistant carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a critical threat to public health, a challenge that was exacerbated by the coronavirus disease 2019 (COVID-19) pandemic. Gap statement. The specific metabolic adaptations that underlie colistin resistance in high-risk sequence type 11 (ST11) CRKP clinical strains, particularly in direct comparison with their susceptible counterparts, remain poorly characterized. Aim. To explore metabolic features associated with colistin resistance in clinical CRKP isolates. Methodology. Twelve CRKP strains, encompassing both colistin-resistant and colistin-susceptible isolates, were analysed for antimicrobial resistance profiles, virulence-associated genes, sequence types and biofilm formation capacity. Comparative untargeted metabolomics was performed to map metabolic shifts between the resistant and susceptible groups. Results. All isolates belonged to the high-risk clone ST11, harboured the KPC-2 carbapenemase and carried multiple virulence genes, with K2 being the dominant serotype. All isolates formed biofilms, with resistant isolates showing enhanced capacity. Colistin resistance was chromosomally mediated by pmrB and mgrB mutations, with no plasmid-encoded mcr genes detected. Untargeted metabolomics identified 126 significantly differentially expressed metabolites (DEMs) between resistant and susceptible isolates. These DEMs were significantly enriched in lipids and lipid-like molecules. Colistin-resistant strains exhibited increased glycerophospholipids, sphingolipids and fatty acids, coupled with decreased metabolites from central carbon and amino acid pathways. Conclusion. In this exploratory study, colistin resistance in these ST11 CRKP strains was associated with chromosomal alterations in pmrB and mgrB and with marked shifts in membrane-associated lipid metabolites. While these metabolic changes suggested membrane remodelling, they remain associative and require functional validation. Beyond resistance, the co-carriage of these traits with robust virulence gene expression highlights a critical clinical challenge, supporting the need for further research into combination therapies targeting these adaptive lipid pathways.

Source: Journal of Medical Microbiology

DOI: 10.1099/jmm.0.002217

Authors: Ling Hao, Xiao Yang, Nadeem Ullah

Institutions: Guangzhou First People's Hospital, South China University of Technology, Umeå University

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: Basic and Applied Basic Research Foundation of Guangdong Province