Cellular efflux transporters and the potential role of natural products in combating efflux mediated drug resistance.
Efflux mediated multidrug resistance (MDR) is a major problem in the treatment of bacterial, fungal and protozoal infections in addition to cancer chemotherapy. Among other well known mechanisms, efflux pumps are significant contributors to chemo-resistance. Efflux mediated resistance generally occurs through up-regulation of genes responsible for the expression of transporter proteins extruding drugs from the cell to create intracellular sub-therapeutic concentrations leading to resistance. The rapid expansion of MDR pathogens necessitates the discovery of resistance modifying drugs, which in combination with antimicrobial or chemotherapeutic agents would tend to reinstate the action of these drugs and avert the emergence of acquired resistance. This review describes the existence of efflux pumps in prokaryotes and eukaryotes as well as their role in chemo-resistance with a special focus on natural product-derived efflux pump inhibitors.
Department of Pharmacy, University of Malakand, Khyber Pakhtoonkhwa, (KP) 18000, Pakistan, ayazuop@gmail.com.
Muhammad
M
Ayaz
Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
Fazal
F
Subhan
Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa (KP) 18000, Pakistan.
Abdul
A
Sadiq
Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa (KP) 18000, Pakistan.
Farhat
F
Ullah
Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU) Peshawar, Pakistan.
Jawad
J
Ahmed
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NU, U.K.
Robert D E
RD
Sewell
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D003141:Communicable Diseases / Q000188:drug therapy / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000502:physiology; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D001688:Biological Products; D026901:Membrane Transport Proteins