Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin

• DOI: 10.1371/journal.ppat.1012705
• Publication Date: 2024-11-21T18:57:07Z
• Authors: Fabiana Bisaro; Clay D. Jackson-L...; Jenna C. McGuffey; Anna J. Hooppaw; Sophie Bodrog; Leila Jebeli; Manon Janet-Maitre; Juan C. Ortiz-Mar...; Tim van Opijnen; Nichollas E. Scott; Gisela Di Venanzio; Mario F. Feldman
• Keywords: Colistin; Acinetobacter baumannii; Diclofenac

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and CDC categorize MDR A . as a top priority for research development new antibiotics. Colistin is last-resort antibiotic carbapenem-resistant Not surprisingly, reintroduction colistin resulted in emergence colistin-resistant strains. Diclofenac nonsteroidal anti-inflammatory drug used pain inflammation associated with arthritis. In this work, we show diclofenac sensitizes strains colistin, vitro murine model pneumonia. also reduced minimal inhibitory concentration (MIC) Klebsiella pneumoniae Pseudomonas aeruginosa Transcriptomic proteomic analyses revealed an upregulation oxidative stress-related genes downregulation type IV pili induced by combination treatment. Notably, concentrations effective were substantially lower than those determined , implying stronger synergistic effect vivo compared pilA mutant strain, lacking primary component pili, became sensitive absence diclofenac. suggest key activity these drugs indicates exert anti-virulence effect. Together, results can be repurposed