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

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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; Plasmodium falciparun; Pseudomonas aeruginosa; antiparasite; chemoresistance; efflux pump; inhibitor; structure-activity relationships; transporter

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709787002619

Affiliations: UMR-MD-1, Transporteurs Membranaires, Chimioresistance et Drug Design, Faculte de Medecine, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France.

Publication date: January 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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