Genetic diversity of Plasmodium vivax metacaspase 1 and Plasmodium vivax multi-drug resistance 1 genes of field isolates from Mauritania, Sudan and Oman. (December 2017)

• Record Type: Journal Article
• Authors: Sow, Fatimata; Bonnot, Guillaume; Ahmed, Bilal; Diagana, Sidi; Kebe, Hachim; Koita, Mohamedou; Samba, Ba; Al-Mukhaini, Said; Al-Zadjali, Majed; Al-Abri, Seif; Ali, Osama; Samy, Abdallah; Hamid, Muzamil; Ali Albsheer, Musab; Simon, Bruno; Bienvenu, Anne-Lise; Petersen, Eskild; Picot, Stéphane
• Is Part Of: Malaria journal. Volume 16:Number 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Plasmodium vivax -- Metacaspases -- PvMCA1-cd -- pvmdr1 gene -- SNP -- Drug resistance -- Apoptose -- Oman -- Mauritania -- Sudan; Malaria -- Periodicals; 616.9362
• DOI: 10.1186/s12936-017-1687-1
• Languages: English
• ISSNs: 1475-2875

Abstract

Abstract Background Plasmodium vivax is the second most important human malaria parasite, widely spread across the world. This parasite is associated with important issues in the process toward malaria elimination, including potential for relapse and increased resistance to chloroquine.Plasmodium vivax multi-drug resistant (pvmdr1 ) is suspected to be a marker of resistance although definitive evidence is lacking. Progress has been made in knowledge of biological factors affecting parasite growth, including mechanisms of regulated cell death and the suspected role of metacaspase.Plasmodium vivax metacaspase1 (PvMCA1-cd) has been described with a catalytic domain composed of histidine (H372) and cysteine (C428) residues. The aim of this study was to test for a link between the conserved histidine and cysteine residues in PvMCA1-cd, and the polymorphism of theP. vivax multi-drug resistant gene (pvmdr1 ). Results ThirtyP. vivax isolates were collected from Mauritania, Sudan, and Oman. Among the 28P. vivax isolates successfully sequenced, only 4 samples showed the conserved His (372)–Cys (428) residues in PvMCA1-cd. Single nucleotide polymorphisms observed were H372T (46.4%), H372D (39.3%), and C428R (85.7%). A new polymorphic catalytic domain was observed at His (282)–Cys (305) residues. Sequences alignment analysis ofpvmdr1 showed SNP in the three codons 958, 976 and 1076. A single SNP was identified at the codon M958Y (60%), 2 SNPs were found at the position 976: Y976F (13%) and Y976V (57%), and 3 SNPs were identified at the position 1076: F1076L (40%), F1076T (53%) and F1076I (3%). Only one isolate was wildtype in all three codons (MYF), 27% were single MYL mutants, and 10% were double MFL mutants. Three new haplotypes were also identified: the triple mutantYVT was most prevalent (53.3%) distributed in the three countries, while tripleYFL andYVI mutants (3%), were only found in samples from Sudan and Mauritania. Conclusions Triple or quadruple mutants for metacaspase genes and double or triple mutants forPvmdr1 were observed in 24/28 and 19/28 samples. There was no difference in the frequency of mutations between PvMCA1-cd andPvmdr1 (P > 0.2). Histidine and cysteine residues in PvMCA1-cd are highly polymorphic and linkage disequilibrium with SNPs ofPvmdr1 gene may be expected from these three areas with different patterns ofP. vivax transmission.