Nontargeted Metabolomics Analysis of Carbapenem-Resistant Pseudomonas aeruginosa

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection is becoming increasingly severe in clinical practice, yet its host metabolic characteristics remain unclear. Based on metabolomics, this study compares the metabolic profiles of patients infected with CRPA versus susceptible strains, aiming to identify potential diagnostic biomarkers and therapeutic targets.

This single-center case-control study enrolled 20 inpatients diagnosed with Pseudomonas aeruginosa infection at the Second People's Hospital between May 2023 and May 2024. Based on antimicrobial susceptibility testing, patients were divided into a CRPA group (n = 10) and a carbapenem-susceptible (CSPA) group (n = 10). Plasma samples from all patients underwent untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry. Differential metabolites were screened by applying principal component analysis, orthogonal partial least squares-discriminant analysis multivariate statistical analysis, and univariate analysis. These metabolites were subsequently annotated and subjected to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Human Metabolome Database, and ChemSpider databases.

Metabolomic analysis identified 19 differentially abundant metabolites, more than half of which were involved in lipid metabolism. This was primarily characterized by the upregulation of glycerophospholipids (such as phosphatidylserine and phosphatidylinositol) and the downregulation of glycerophosphocholine, phosphatidylethanolamine, and certain sphingolipids. Beyond lipids, compounds such as cholic acids, p-cresol sulfate, and hippuric acid were also significantly upregulated. KEGG enrichment analysis revealed that the differential metabolites were predominantly enriched in pathways related to glycerophospholipid metabolism, sphingolipid metabolism, and ether lipid metabolism, indicating that disrupted lipid metabolism is a core metabolic feature of CRPA infection.

This study demonstrates that the metabolic differences in CRPA-infected patients are concentrated in lipid metabolism, suggesting a close association between drug-resistant infections and host-pathogen lipid metabolic remodeling. Changes in relevant lipids hold value as potential diagnostic and prognostic biomarkers, while lipid metabolic pathways may also represent novel targets for future therapeutic interventions.