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ABC systems are one of the largest described protein superfamilies. These systems have a domain organization that may contain 1 or more transmembrane domains (ABC_TM1F) and 1 or 2 ATP-binding domains (ABC_2). The functions (e.g., import, export and DNA repair) of these proteins distinguish the 3 classes of ABC systems. Mining and PCR-based cloning were used to identify 33 putative ABC systems from the Brugia malayi genome. There were 31 class 2 genes, commonly called ABC transporters, and 2 class 3 genes. The ABC transporters were divided into subfamilies. Three belonged to subfamily A, 16 to subfamily B, 5 to subfamily C, 1 to subfamily E and 3 to subfamilies F and G, respectively. None were placed in subfamilies D and H. Similar to other ABC systems, the ABC_2 domain of B. malayi genes was conserved and contained the Walker A and B motifs, the signature sequence/linker region and the switch region with the conserved histidine. The ABC_TM1F domain was less conserved. The relative abundance of ABC systems was quantified using real-time reverse transcription PCR and was significantly higher in female adults of B. malayi than in males and microfilaria, particularly those in subfamilies B and C, which are associated with drug resistance.

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.

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Kidney International (2016) 89, 251-252; http://dx.