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

Malaria Journal

Research

Said K. Al-Mukhaini¹  Majed Al-Zadjali¹  Seif S. Al-Abri¹  Osama A. M. Ali¹  Eskild Petersen²  Muzamil Mahdi Abdel Hamid³  Musab M. Ali Albsheer³  Abdallah M. Samy⁴  Fatimata Sow⁵  Guillaume Bonnot⁵  Anne-Lise Bienvenu⁶  Bruno Simon⁶  Stéphane Picot⁶  Ba Malado Samba⁷  Sidi Mohamed Diagana⁸  Bilal Rabah Ahmed⁸  Mohamedou Koita⁹  Hachim Kebe^1,10 

[1] Department of Infectious Diseases, The Royal Hospital, Muscat, Oman;Department of malaria, Ministry of Health, Muscat, Oman;Department of Infectious Diseases, The Royal Hospital, Muscat, Oman;Department of malaria, Ministry of Health, Muscat, Oman;Institute of Clinical Medicine, Faculty of Health Science, University of Aarhus, Aarhus, Denmark;Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, Medical Campus, University of Khartoum, P.O. BOX 102, Qassr Street, Khartoum, Sudan;Entomology Department, Faculty of Science, Ain Shams University, Abbassia, 11566, Cairo, Egypt;Biodiversity Institute, University of Kansas, 66045, Lawrence, KS, USA;Institut de Chimie et Biochimie Moléculaires et Supramoléculaires ICBMS-UMR5246, CNRS-INSA-CPE, Malaria Research Unit, University Claude Bernard Lyon 1, 43 Boulevard du 11 novembre 1918, 69622, Lyon, Villeurbane, France;Institut de Chimie et Biochimie Moléculaires et Supramoléculaires ICBMS-UMR5246, CNRS-INSA-CPE, Malaria Research Unit, University Claude Bernard Lyon 1, 43 Boulevard du 11 novembre 1918, 69622, Lyon, Villeurbane, France;Institut of Parasitology and Medical Mycology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Laboratoire Analyse de Biologie Médicale du Centre hospitalier de Rosso Mauritanie, BP-41, Rosso, Mauritania;Laboratoire de Bactériologie et Parasitologie de l’Hôpital Cheikh Zayed, BP-5720, Nouakchott, Mauritania;Laboratoire de Parasitologie et de Mycologie Médicale Institut National de Recherches en Santé Publique (INRSP), Avenue Jemal AbdeNasser, BP-695, Nouakchott, Mauritania;Service des Maladies Infectieuses et Tropicales, Centre Hospitalier National de Nouakchott, BP-612, Nouakchott, Mauritania;

关键词: Plasmodium vivax;    Metacaspases;    PvMCA1-cd;    pvmdr1;    SNP;    Drug resistance;    Apoptose;    Oman;    Mauritania;    Sudan;   

DOI  :  10.1186/s12936-017-1687-1

 received in 2016-10-28, accepted in 2017-01-10,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPlasmodium 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).ResultsThirty 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.ConclusionsTriple 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.

【 授权许可】

CC BY   
© The Author(s) 2017