Polymorphism in ABC transporter genes of Dirofilaria immitis
| Autor: | Roger K. Prichard, Catherine Bourguinat, Thangadurai Mani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genotype Dirofilaria immitis Single-nucleotide polymorphism ATP-binding cassette transporter Biology P-glycoprotein Polymorphism Single Nucleotide Article lcsh:Infectious and parasitic diseases 03 medical and health sciences Animals Pharmacology (medical) lcsh:RC109-216 Gene Genotyping Pharmacology Genetics Genome Helminth Computational Biology Sterol transport 3. Good health Single nucleotide polymorphism Multiple drug resistance 030104 developmental biology Infectious Diseases biology.protein Heartworm Parasitology ATP-Binding Cassette Transporters Efflux ABC transporter |
| Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance, Vol 7, Iss 2, Pp 227-235 (2017) International Journal for Parasitology: Drugs and Drug Resistance |
| ISSN: | 2211-3207 |
| Popis: | Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and occasionally in humans. Prevention of the disease has been mainly by monthly use of the macrocyclic lactone (ML) endectocides during the mosquito transmission season. Recently, ML resistance has been confirmed in D. immitis and therefore, there is a need to find new classes of anthelmintics. One of the mechanisms associated with ML resistance in nematodes has been the possible role of ATP binding cassette (ABC) transporters in reducing drug concentrations at receptor sites. ABC transporters, mainly from sub-families B, C and G, may contribute to multidrug resistance (MDR) by active efflux of drugs out of the cell. Gene products of ABC transporters may thus serve as the targets for agents that may modulate susceptibility to drugs, by inhibiting drug transport. ABC transporters are believed to be involved in a variety of physiological functions critical to the parasite, such as sterol transport, and therefore may also serve as the target for drugs that can act as anthelmintics on their own. Knowledge of polymorphism in these ABC transporter genes in nematode parasites could provide useful information for the process of drug design. We have identified 15 ABC transporter genes from sub-families A, B, C and G, in D. immitis, by comparative genomic approaches and analyzed them for polymorphism. Whole genome sequencing data from four ML susceptible (SUS) and four loss of efficacy (LOE) pooled populations were used for single nucleotide polymorphism (SNP) genotyping. Out of 231 SNPs identified in those 15 ABC transporter genes, 89 and 75 of them were specific to the SUS or LOE populations, respectively. A few of the SNPs identified may affect gene expression, protein function, substrate specificity or resistance development and may be useful for transporter inhibitor/anthelmintic drug design, or in order to anticipate resistance development. Graphical abstract Image 1 Highlights • In the D. immitis genome, all ABC-A, -B, -C and -G transporter genes were identified. • Within 15 ABC transporter genes identified in D. immitis, 231 SNP loci were found. • Four exonic SNPs caused changes in predicted secondary structure of ABC proteins. • D. immitis populations have low genetic variability among ABC transporter genes. |
| Databáze: | OpenAIRE |
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