Metabolic response of Klebsiella oxytoca to ciprofloxacin exposure: a metabolomics approach.

Autor: Ahmed S; Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.; Department of Environment and Quality Control, Kurdistan Institution for Strategic Studies and Scientific Research, Sulaymaniyah, Kurdistan Region, Iraq., Shams S; Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom., Trivedi D; Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.; Clinical Metabolomics Unit, Institute of Developmental Sciences, University of Southampton, Southampton, UK., Lima C; Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom., McGalliard R; Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, L69 7BE, United Kingdom., Parry CM; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK., Carrol ED; Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, L69 7BE, United Kingdom., Muhamadali H; Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom., Goodacre R; Centre for Metabolomics Research, Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, United Kingdom. roy.goodacre@liverpool.ac.uk.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2024 Dec 15; Vol. 21 (1), pp. 8. Date of Electronic Publication: 2024 Dec 15.
DOI: 10.1007/s11306-024-02206-y
Abstrakt: Introduction: Rapid detection and identification of pathogens and antimicrobial susceptibility is essential for guiding appropriate antimicrobial therapy and reducing morbidity and mortality associated with sepsis.
Objectives: The metabolic response of clinical isolates of Klebsiella oxytoca exposed to different concentrations of ciprofloxacin (the second generation of quinolones antibiotics) were studied in order to investigate underlying mechanisms associated with antimicrobial resistance (AMR).
Methods: Metabolomics investigations were performed using Fourier-transform infrared (FT-IR) spectroscopy as a metabolic fingerprinting approach combined with gas chromatography-mass spectrometry (GC-MS) for metabolic profiling.
Results: Our findings demonstrated that metabolic fingerprints provided by FT-IR analysis allowed for the differentiation of susceptible and resistant isolates. GC-MS analysis validated these findings, while also providing a deeper understanding of the metabolic alterations caused by exposure to ciprofloxacin. GC-MS metabolic profiling detected 176 metabolic features in the cellular extracts cultivated on BHI broth, and of these, 137 could be identified to Metabolomics Standards Initiative Level 2. Data analysis showed that 40 metabolites (30 Level 2 and 10 unknown) were differentiated between susceptible and resistant isolates. The identified metabolites belonging to central carbon metabolism; arginine and proline metabolism; alanine, aspartate and glutamate metabolism; and pyruvate metabolism. Univariate receiver operating characteristic (ROC) curve analyses revealed that six of these metabolites (glycerol-3-phosphate, O-phosphoethanolamine, asparagine dehydrate, maleimide, tyrosine, and alanine) have a crucial role in distinguishing susceptible from resistant isolates (AUC > 0.84) and contributing to antimicrobial resistance in K. oxtytoca.
Conclusion: Our study provides invaluable new insights into the mechanisms underlying development of antimicrobial resistance in K. oxytoca suggests potential therapeutic targets for prevention and identification of AMR in K. oxytoca infections.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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