Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum

Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mit...

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Main Authors: Ibraheem, Zaid O., Abd. Majid, Roslaini, Mohd. Noor, Sabariah, Mohd. Sedik, Hasidah, Basir, Rusliza
Format: Article
Language:English
Published: Hindawi Publishing Corporation 2014
Online Access:http://psasir.upm.edu.my/id/eprint/35291/
http://psasir.upm.edu.my/id/eprint/35291/1/Role%20of%20Different%20Pf%20crt%20and%20Pf%20mdr-1%20Mutations%20in%20Conferring.pdf
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author Ibraheem, Zaid O.
Abd. Majid, Roslaini
Mohd. Noor, Sabariah
Mohd. Sedik, Hasidah
Basir, Rusliza
author_facet Ibraheem, Zaid O.
Abd. Majid, Roslaini
Mohd. Noor, Sabariah
Mohd. Sedik, Hasidah
Basir, Rusliza
author_sort Ibraheem, Zaid O.
building UPM Institutional Repository
collection Online Access
description Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.
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spelling upm-352912016-02-18T08:06:43Z http://psasir.upm.edu.my/id/eprint/35291/ Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum Ibraheem, Zaid O. Abd. Majid, Roslaini Mohd. Noor, Sabariah Mohd. Sedik, Hasidah Basir, Rusliza Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs. Hindawi Publishing Corporation 2014 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/35291/1/Role%20of%20Different%20Pf%20crt%20and%20Pf%20mdr-1%20Mutations%20in%20Conferring.pdf Ibraheem, Zaid O. and Abd. Majid, Roslaini and Mohd. Noor, Sabariah and Mohd. Sedik, Hasidah and Basir, Rusliza (2014) Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum. Malaria Research and Treatment, 2014. art. no. 950424. pp. 1-17. ISSN 2090-8075; ESSN: 2044-4362 http://www.hindawi.com/journals/mrt/2014/950424/abs/ 10.1155/2014/950424
spellingShingle Ibraheem, Zaid O.
Abd. Majid, Roslaini
Mohd. Noor, Sabariah
Mohd. Sedik, Hasidah
Basir, Rusliza
Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum
title Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum
title_full Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum
title_fullStr Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum
title_full_unstemmed Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum
title_short Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum
title_sort role of different pfcrt and pfmdr-1 mutations in conferring resistance to antimalaria drugs in plasmodium falciparum
url http://psasir.upm.edu.my/id/eprint/35291/
http://psasir.upm.edu.my/id/eprint/35291/
http://psasir.upm.edu.my/id/eprint/35291/
http://psasir.upm.edu.my/id/eprint/35291/1/Role%20of%20Different%20Pf%20crt%20and%20Pf%20mdr-1%20Mutations%20in%20Conferring.pdf