Antimicrobial and Anti-Efflux Machinery of FDA-Approved Proton Pump Inhibitors and Vitamins Against and .

Background: The efflux system is one of the resistance mechanisms that bacteria use to reduce the effectiveness of antibiotics, leading to the development of multidrug resistance. To evaluate other treatment choices, esomeprazole (ESO), omeprazole (OME), pantoprazole (PAN), vitamin D (VD), and vitamin K (VK) were tested for potential efflux pump (EP)-inhibiting activity.

Methods: The minimum inhibitory concentrations (MICs) of the tested drugs were determined against ATCC 51503 and PAO1. Quantitative estimation of the EP-inhibiting activity of the tested medications was phenotypically investigated with a semi-automated fluorometric system and genotypically confirmed by real-time polymerase chain reaction (RT-PCR). Data were confirmed through docking study.

Results: ATCC 51503 and PAO1 were positive efflux standard strains. VD and VK revealed an MIC of 625-1250 µg/mL and MIC of 2500-5000 µg/mL, lower than what was detected for PPIs (MIC = 16,000-32,000 µg/mL). Vitamins showed powerful anti-efflux activity with remarkable ethidium bromide accumulation in ATCC 51503 and PAO1. Also, VD and VK significantly lowered the MIC of ciprofloxacin by 64-fold. On the molecular level, OME showed a notable decrease in the relative expression of the efflux-encoding genes and by 91.5% and 99.7% in ATCC 51503 and PAO1, respectively.

Conclusion: This study highlights the anti-efflux activity of ESO, OME, PAN, VD, and VK against the tested Gram-negative strains. Hence, these PPIs and vitamins could be valuable adjuvant treatments to enhance the effectiveness of curing infections caused by MDR strains.