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

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 resi...

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Published in:	Malaria journal Vol. 16; no. 1; p. 61
Main Authors:	Sow, Fatimata, Bonnot, Guillaume, Ahmed, Bilal Rabah, Diagana, Sidi Mohamed, Kebe, Hachim, Koita, Mohamedou, Samba, Ba Malado, Al-Mukhaini, Said K, Al-Zadjali, Majed, Al-Abri, Seif S, Ali, Osama A M, Samy, Abdallah M, Hamid, Muzamil Mahdi Abdel, Ali Albsheer, Musab M, Simon, Bruno, Bienvenu, Anne-Lise, Petersen, Eskild, Picot, Stéphane
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 02-02-2017 BioMed Central
Subjects:	Analysis Apoptosis Cell death Chloroquine Cloning Codons Cysteine Deoxyribonucleic acid DNA Drug resistance Drugs Gene polymorphism Genes Genetic aspects Genetic diversity Genetic variation Genomes Haplotypes Histidine Human diseases Identification Infections Linkage disequilibrium Malaria Mauritania Multidrug resistance Multidrug Resistance-Associated Proteins - genetics Mutants Mutation Nucleotides Oman Parasites Plasmodium vivax Plasmodium vivax - genetics Polymorphism Polymorphism, Genetic Polymorphism, Single Nucleotide Protozoan Proteins - genetics Residues Single-nucleotide polymorphism Studies Sudan Vector-borne diseases Oman Mauritania Pakistan Asia Africa Sudan Brazil France Ethiopia Indonesia India Plasmodium vivax pvmdr1 gene Mauritania Metacaspases SNP Sudan Drug resistance Apoptose Oman PvMCA1-cd
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Summary:	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 the P. vivax multi-drug resistant gene (pvmdr1). Thirty P. vivax isolates were collected from Mauritania, Sudan, and Oman. Among the 28 P. 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 of pvmdr1 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 mutant YVT was most prevalent (53.3%) distributed in the three countries, while triple YFL and YVI mutants (3%), were only found in samples from Sudan and Mauritania. Triple or quadruple mutants for metacaspase genes and double or triple mutants for Pvmdr1 were observed in 24/28 and 19/28 samples. There was no difference in the frequency of mutations between PvMCA1-cd and Pvmdr1 (P > 0.2). Histidine and cysteine residues in PvMCA1-cd are highly polymorphic and linkage disequilibrium with SNPs of Pvmdr1 gene may be expected from these three areas with different patterns of P. vivax transmission.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1475-2875 1475-2875
DOI:	10.1186/s12936-017-1687-1