Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane
Abstract Background The spread of drug resistance has been a major obstacle to the control of malaria. The mechanisms underlying drug resistance in malaria seem to be complex and multigenic. The current literature on multiple drug resistance against anti-malarials has documented PfMDR1, an ATP-bindi...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2009
|
Subjects: | |
Online Access: | https://doi.org/10.1186/1475-2875-8-205 https://doaj.org/article/8871ff9fec1f4de49cd9e1c7bfe5dd76 |
id |
ftdoajarticles:oai:doaj.org/article:8871ff9fec1f4de49cd9e1c7bfe5dd76 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:8871ff9fec1f4de49cd9e1c7bfe5dd76 2023-05-15T15:12:03+02:00 Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane Luty Adrian JF van de Vegte-Bolmer Marga van den Heuvel Jeroen MW Kavishe Reginald A Russel Frans GM Koenderink Jan B 2009-08-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-205 https://doaj.org/article/8871ff9fec1f4de49cd9e1c7bfe5dd76 EN eng BMC http://www.malariajournal.com/content/8/1/205 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-205 1475-2875 https://doaj.org/article/8871ff9fec1f4de49cd9e1c7bfe5dd76 Malaria Journal, Vol 8, Iss 1, p 205 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-205 2022-12-31T06:55:17Z Abstract Background The spread of drug resistance has been a major obstacle to the control of malaria. The mechanisms underlying drug resistance in malaria seem to be complex and multigenic. The current literature on multiple drug resistance against anti-malarials has documented PfMDR1, an ATP-binding cassette (ABC) protein, as an important determinant of resistance. In the Plasmodium falciparum genome, there are several ABC transporters some of which could be putative drug transporting proteins. In order to understand the molecular mechanisms underlying drug resistance, characterization of these transporters is essential. The aim of this study was to characterize and localize putative ABC transporters. Methods In the plasmoDB database, 16 members of the P. falciparum ABC family can be identified, 11 of which are putative transport proteins. A phylogenetic analysis of the aligned NBDs of the PfABC genes was performed. Antibodies against PfMRP1 (PfABCC1), PfMRP2 (PfABCC2), and PfMDR5 (PfABCB5) were generated, affinity purified and used in immunocytochemistry to localize the proteins in the asexual stages of the parasite. Results The ABC family members of P. falciparum were categorized into subfamilies. The ABC B subfamily was the largest and contained seven members. Other family members that could be involved in drug transport are PfABCC1, PfABCC2, PfABCG1, and PfABCI3. The expression and localization of three ABC transport proteins was determined. PfMRP1, PfMRP2, and PfMDR5 are localized to the plasma membrane in all asexual stages of the parasite. Conclusion In conclusion, 11 of the 16 ABC proteins in the P. falciparum genome are putative transport proteins, some of which might be involved in drug resistance. Moreover, it was demonstrated that three of these proteins are expressed on the parasite's plasma membrane. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 205 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Luty Adrian JF van de Vegte-Bolmer Marga van den Heuvel Jeroen MW Kavishe Reginald A Russel Frans GM Koenderink Jan B Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The spread of drug resistance has been a major obstacle to the control of malaria. The mechanisms underlying drug resistance in malaria seem to be complex and multigenic. The current literature on multiple drug resistance against anti-malarials has documented PfMDR1, an ATP-binding cassette (ABC) protein, as an important determinant of resistance. In the Plasmodium falciparum genome, there are several ABC transporters some of which could be putative drug transporting proteins. In order to understand the molecular mechanisms underlying drug resistance, characterization of these transporters is essential. The aim of this study was to characterize and localize putative ABC transporters. Methods In the plasmoDB database, 16 members of the P. falciparum ABC family can be identified, 11 of which are putative transport proteins. A phylogenetic analysis of the aligned NBDs of the PfABC genes was performed. Antibodies against PfMRP1 (PfABCC1), PfMRP2 (PfABCC2), and PfMDR5 (PfABCB5) were generated, affinity purified and used in immunocytochemistry to localize the proteins in the asexual stages of the parasite. Results The ABC family members of P. falciparum were categorized into subfamilies. The ABC B subfamily was the largest and contained seven members. Other family members that could be involved in drug transport are PfABCC1, PfABCC2, PfABCG1, and PfABCI3. The expression and localization of three ABC transport proteins was determined. PfMRP1, PfMRP2, and PfMDR5 are localized to the plasma membrane in all asexual stages of the parasite. Conclusion In conclusion, 11 of the 16 ABC proteins in the P. falciparum genome are putative transport proteins, some of which might be involved in drug resistance. Moreover, it was demonstrated that three of these proteins are expressed on the parasite's plasma membrane. |
format |
Article in Journal/Newspaper |
author |
Luty Adrian JF van de Vegte-Bolmer Marga van den Heuvel Jeroen MW Kavishe Reginald A Russel Frans GM Koenderink Jan B |
author_facet |
Luty Adrian JF van de Vegte-Bolmer Marga van den Heuvel Jeroen MW Kavishe Reginald A Russel Frans GM Koenderink Jan B |
author_sort |
Luty Adrian JF |
title |
Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane |
title_short |
Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane |
title_full |
Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane |
title_fullStr |
Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane |
title_full_unstemmed |
Localization of the ATP-binding cassette (ABC) transport proteins PfMRP1, PfMRP2, and PfMDR5 at the Plasmodium falciparum plasma membrane |
title_sort |
localization of the atp-binding cassette (abc) transport proteins pfmrp1, pfmrp2, and pfmdr5 at the plasmodium falciparum plasma membrane |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-205 https://doaj.org/article/8871ff9fec1f4de49cd9e1c7bfe5dd76 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 205 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/205 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-205 1475-2875 https://doaj.org/article/8871ff9fec1f4de49cd9e1c7bfe5dd76 |
op_doi |
https://doi.org/10.1186/1475-2875-8-205 |
container_title |
Malaria Journal |
container_volume |
8 |
container_issue |
1 |
container_start_page |
205 |
_version_ |
1766342792278179840 |