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

Abstract

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.

Metabolic Changes in Pseudomonas oleovorans Isolated from Contaminated Construction Material Exposed to Varied Biocide Treatments

“…It is also involved in the elimination of cellular metabolic byproducts. L-carnitine is involved in regulating stress responses, energy metabolism, and protein folding, irrespective of whether bacteria inhabit aerobic or anaerobic environments [ 46 ]. An important function of L-carnitine is its ability to mitigate osmotic stress in bacteria by acting as an osmolyte, thus helping maintain cellular fluid levels and preventing cellular damage [ 47 ].…”

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives

“…In the context of CF, pulmonary biomarkers are increasingly employed to examine disease action and assess the response to therapy in individuals [95]. Recently, Su et al [96] conducted research indicating that an increased biosynthesis of fatty acids plays a crucial role in CFX resistance development in P. aeruginosa. Their study revealed that the elevated fatty acid formation is a distinctive property of metabolomes resistant to CFX, augmented by heightened gene expression and enzymatic action within the biochemical network.…”

“…These findings underscore the significance of increased fatty acid biosynthesis in the CFX resistance of P. aeruginosa, offering a potential target cascade for addressing CFX-resistant strains of the bacteria. The discovery of novel biomarkers is inevitable for enhancing the remedy of CF in patients [96].…”