Expanded applications of omeprazole: Synergistic reversal of colistin resistance in Acinetobacter baumannii

Objectives: Acinetobacter baumannii (A. baumannii) is an opportunistic microorganism capable of triggering life-threatening infections. The rising prevalence of multidrug-resistant A. baumannii in clinical settings has complicated treatment efforts. Colistin serves as the last-line therapy against multidrug-resistant A. baumannii. However, its resurgence has accelerated antimicrobial resistance. To address escalating resistance and stagnant drug development, repurposing clinical drugs for Antibacterial applications shows significant promise. Omeprazole, a Proton Pump Inhibitor, is widely used to treat digestive system disorders.

Methods: This study demonstrated that the combination of omeprazole and colistin exhibits considerable Antibacterial activity through checkerboard susceptibility assays, time-killing experiments, and live/dead Bacterial cell viability tests.

Results: In vivo experiments using a mouse leg Infection model confirmed the synergistic Antibacterial effect. Further mechanistic investigations have disclosed that this combined medication exerts its Antibacterial effect by inducing Bacterial death through the accumulation of Reactive Oxygen Species and subsequent oxidative stress, by inhibiting the formation of biofilms, and by suppressing the expression of drug efflux pumps.

Conclusions: Overall, this study discovered that the clinical drug omeprazole has the potential to act as an Adjuvant to colistin, synergistically reversing colistin resistance in A. baumannii and providing a novel therapeutic strategy for the treatment of infections caused by this pathogen.

Acinetobacter baumannii; Antibiofilm; Colistin; Efflux pump; Omeprazole.