caa a22 4500 445341203 CHVBK 20180317142813.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00436-011-2378-4 doi (NATIONALLICENCE)springer-10.1007/s00436-011-2378-4 The role of Brugia malayi ATP-binding cassette (ABC) transporters in potentiating drug sensitivity [Elektronische Daten] [Jeffrey Tompkins, Laurel Stitt, Alana Morrissette, Bernadette Ardelli] ATP binding cassette (ABC) systems are a diverse group of proteins that have been identified in every organism, from bacteria to humans. Analysis of nematode genomes indicates that the number and arrangement of ABC systems are similar to other organisms, with the majority being ABC transporters. There are few functional studies of ABC transporters in parasitic nematodes; most reports have been on their identification or use as genetic markers to monitor drug resistance. In eukaryotes, some ABC transporters function in tissue defense by actively removing drugs, thus preventing their accumulation. The overexpression of ABC transporters that function as efflux pumps, such as P-glycoprotein (PGP) and the multidrug resistance associated protein (MRP) are known to confer resistance. Drug sensitivity can be restored by administration of PGP interfering or MDR reversal agents. The objective of this study was to determine if ABC systems in filarioid nematodes function similarly to those of other organisms. The relative expression of 33 ABC systems identified in Brugia malayi was quantified following exogenous exposure to the commonly used drug ivermectin (IVM). Following exposure of adults and microfilariae to IVM, there was a significant increase in the transcriptional profiles of a number of ABC systems, mostly within the PGP and MRP subgroups. Coadministration of PGP-interfering and MDR-reversal agents with IVM potentiated sensitivity to the drug in adults and microfilariae. The results suggest that B. malayi ABC transporters function similarly to those in other organisms and are a factor in determining drug sensitivity. Springer-Verlag, 2011 Tompkins Jeffrey Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut Stitt Laurel Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut Morrissette Alana Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut Ardelli Bernadette Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut Parasitology Research Springer-Verlag 109/5(2011-11-01), 1311-1322 0932-0113 109:5<1311 2011 109 436 https://doi.org/10.1007/s00436-011-2378-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00436-011-2378-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tompkins Jeffrey Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut NATIONALLICENCE 700 1- Stitt Laurel Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut NATIONALLICENCE 700 1- Morrissette Alana Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut NATIONALLICENCE 700 1- Ardelli Bernadette Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, R7A 6A9, Brandon, MB, Canada aut NATIONALLICENCE 773 0- Parasitology Research Springer-Verlag 109/5(2011-11-01), 1311-1322 0932-0113 109:5<1311 2011 109 436 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer