Exploring phytochemicals as efflux pump inhibitors against multidrug-resistant bacteria

Summary

Antimicrobial resistance (AMR) is a global problem affecting multiple sectors, ranging from the health sector to the food production sector. Efflux pumps are known as an important resistance mechanism in bacteria, as these efflux pumps pump out the antimicrobials from the cell, thereby making antimicrobial treatment less effective. Plants have been proposed as an interesting source of efflux pump inhibitors (EPIs). This PhD research highlighted the discovery of phytochemicals from edible plant families (Fabaceae and Brassicaceae) as potential EPIs against two major multidrug-resistant (MDR) bacteria, Staphylococcus aureus and Escherichia coli. This study discovered prenylated (iso)flavonoids from Fabaceae as promising inhibitors against NorA efflux pumps in S. aureus, and camalexin, an indole alkaloid from Brassicaceae as inhibitors against AcrB efflux pumps in E. coli. The exploration of phytochemicals from edible plants represents an important stepping stone in the discovery and development of EPIs, particularly for their use as resistance-modifying agents in healthcare or food sectors.