Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling

Jones, PM; George, AM

Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling

Jones, PM George, AM

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Publication Type:: Journal Article
Citation:: International Journal for Parasitology, 2005, 35 (5), pp. 555 - 566
Issue Date:: 2005-04-30

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Field	Value	Language
dc.contributor.author	Jones, PM	en_US
dc.contributor.author	George, AM https://orcid.org/0000-0003-4691-8960	en_US
dc.date.available	2005-01-10	en_US
dc.date.issued	2005-04-30	en_US
dc.identifier.citation	International Journal for Parasitology, 2005, 35 (5), pp. 555 - 566	en_US
dc.identifier.issn	0020-7519	en_US
dc.identifier.uri	http://hdl.handle.net/10453/3910
dc.description.abstract	Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein. © 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.	en_US
dc.relation.ispartof	International Journal for Parasitology	en_US
dc.relation.isbasedon	10.1016/j.ijpara.2005.01.012	en_US
dc.subject.classification	Mycology & Parasitology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Parasites	en_US
dc.subject.mesh	ATP-Binding Cassette Transporters	en_US
dc.subject.mesh	ATP-Binding Cassette, Sub-Family B, Member 1	en_US
dc.subject.mesh	ATP Binding Cassette Transporter, Subfamily B, Member 1	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Computational Biology	en_US
dc.subject.mesh	Drug Resistance, Multiple	en_US
dc.subject.mesh	Genes, MDR	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Sequence Homology	en_US
dc.title	Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.citation.volume	35	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	0707 Veterinary Sciences	en_US
utslib.for	0608 Zoology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	35	en_US

Abstract:

Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein. © 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/3910