Efflux Mechanism, an Attractive Target to Combat Multidrug Resistant Plasmodium falciparum and Pseudomonas aeruginosa

Sandrine      Alibert-Franco; Bruno      Pradines; Abdallah      Mahamoud; Anne      Davin-Regli; Jean-Marie      Pages

doi:10.2174/092986709787002619

Abstract

Chemoresistance is a general health problem concerning infectious diseases and cancer treatments. In this context, the worldwide dissemination of pandrug and multidrug resistant pathogens has severely compromised the efficacy of our antimicrobial weapons and dramatically increased the occurence of therapeutic failure. To efficiently combat multi-resistant pathogens, it is necessary to clearly define the molecular basis of the general resistance mechanism associated with the expression of active efflux pumps, which strongly restrict the intracellular concentration of antimicrobial drugs. Several families of efflux systems capable of multiple drug extrusion have been described. The activity of some efflux systems requires ATP hydrolysis for drug transport while others require a sodium or proton antiport. In this review we focus on two important human pathogens, Plasmodium falciparum and Pseudomonas aeruginosa, which exhibit a high level of antimicrobial resistance associated with the expression of efflux mechanisms. The efflux mechanisms and the development of efflux pump inhibitors (EPIs) are discussed regarding these two pathogens.

Keywords: Antibiotic, antiparasite, chemoresistance, efflux pump, inhibitor, transporter, Plasmodium falciparun, Pseudomonas aeruginosa, structure-activity relationships