Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in Pseudomonas aeruginosa

Autor: Yu-bin Su, Xi-kang Tang, Ling-ping Zhu, Ke-xin Yang, Li Pan, Hui Li, Zhuang-gui Chen
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Microbiology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-302X
DOI: 10.3389/fmicb.2022.845173
Popis: Antibiotic-resistant Pseudomonas aeruginosa is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography–mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant P. aeruginosa strains that originated from P. aeruginosa ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16CIP, PA-R64CIP, and PA-R128CIP, respectively) higher than the original value, compared to CIP-sensitive P. aeruginosa (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128CIP and clinically multidrug-resistant P. aeruginosa strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant P. aeruginosa strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of P. aeruginosa and provide a target pathway for combating CIP-resistant P. aeruginosa.
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