Inventory and analysis of ATP-binding cassette (ABC) systems inBrugia malayi

Abstract

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.

Synergism between ivermectin and the tyrosine kinase/ P -glycoprotein inhibitor crizotinib against Haemonchus contortus larvae in vitro

“…Multiple ABC transporter genes have been reported in free-living and parasitic nematodes (Sheps et al, 2004;Ardelli et al, 2010;Laing et al, 2013). The overexpression of some of these transporters has been observed in drug-resistant isolates of different nematode species compared to susceptible reference isolates (Dicker et al, 2011;Williamson et al, 2011;Sarai et al, 2013;Raza et al, 2016), suggesting a potential role for ABC transporters in anthelmintic resistance.…”

The role of drug efflux systems in anthelmintic resistance in parasitic nematodes

“…There have been various reports describing the presence of genes that encode different ABC transporters in nematodes including H. contortus (Laing et al, 2013), C. elegans , Brugia malayi (Ardelli et al, 2010), Te. circumcincta (Dicker et al, 2011) and O. volvulus (Huang and Prichard, 1999).…”

“…C. elegans is known to have 15 P-gp genes (pgp), eight MRP (mrp) and nine HAF genes (haf) . In parasitic nematodes, eight P-gp, five MRPs and eight HAF transporter genes were reported in Brugia malayi (Ardelli et al, 2010), two P-gp genes in cyathostomins (Drogemuller et al, 2004), 11 partial sequences of P-gp genes in Te. circumcincta (Dicker et al, 2011) and four P-gp and three HAF encoding genes have been reported in Onchocerca volvulus (Huang and Prichard, 1999;Bourguinat et al, 2008).…”

“…Multiple ABC transporter genes have been reported in free-living and parasitic nematodes Ardelli et al, 2010;Laing et al, 2013). The overexpression of some of these transporters has been observed in drug-resistant isolates of different nematode species compared to susceptible reference isolates (Dicker et al, 2011;Williamson et al, 2011;Sarai et al, 2013;Raza et al, 2016a), suggesting a potential role for ABC transporters in anthelmintic resistance.…”

“…Furthermore, eight P-gp genes, five MRP genes and eight HAF genes were identified in Brugia malayi (Ardelli et al, 2010), two P-gp genes in cyathostomins (Drogemuller et al, 2004) and 11 partial sequences of P-gp genes have been reported in Teladorsagia circumcincta (Dicker et al, 2011). The diversity of nematode P-gps suggests that they may play a protective role in the efflux of a wide range of environmental toxins and internal metabolites (Prichard and Roulet, 2007).…”