Efflux Pump Inhibitors Derived From Natural Sources as Novel Antibacterial Agents Against Pseudomonas aeruginosa: A Review

Pseudomonas aeruginosa is one of the most important opportunistic human pathogen that can lead to serious nosocomial infections. The treatment of pseudomonas infections due to the high emergence of resistance to antimicrobial agents is challenging. One of the mechanisms of antibiotic resistance in P. aeruginosa is the active efflux pumps. To date, 11 different efflux pumps of the RND family in P. aeruginosa that enable the efflux of antibiotics/anti-microbial production have been detected. These pumps include MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexGHI-OpmD, MexJK-OprM/OpmH, MexMN, MexPQ-OpmE, MexVW-OprM, MexXY-OprM, TriABC-OpmH, and MuxABC-OpmB. Recently, Efflux Pump Inhibitors (EPIs) have been considered as novel antimicrobial agents to overcome drug efflux mechanisms of bacterial pathogens. In recent years, numerous EPIs have been identified or synthesized for multi-drug resistant (MDR) bacteria; these include existing pharmacologic drugs, naturally occurring compounds, and synthetic derivatives thereof. This review describes the current progress in the assessment and development of EPI for using against P. aeruginosa.