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 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.
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, Lyon, 69622, Villeurbane, France. fatimata.sow@etu.univ-lyon1.fr.
Fatimata
0000-0003-0154-2349
F
Sow
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, Lyon, 69622, Villeurbane, France.
Guillaume
G
Bonnot
Laboratoire de Bactériologie et Parasitologie de l'Hôpital Cheikh Zayed, BP-5720, Nouakchott, Mauritania.
Bilal Rabah
BR
Ahmed
Laboratoire de Bactériologie et Parasitologie de l'Hôpital Cheikh Zayed, BP-5720, Nouakchott, Mauritania.
Sidi Mohamed
SM
Diagana
Service des Maladies Infectieuses et Tropicales, Centre Hospitalier National de Nouakchott, BP-612, Nouakchott, Mauritania.
Hachim
H
Kebe
Laboratoire de Parasitologie et de Mycologie Médicale Institut National de Recherches en Santé Publique (INRSP), Avenue Jemal AbdeNasser, BP-695, Nouakchott, Mauritania.
Mohamedou
M
Koita
Laboratoire Analyse de Biologie Médicale du Centre hospitalier de Rosso Mauritanie, BP-41, Rosso, Mauritania.
Ba Malado
BM
Samba
Department of Infectious Diseases, The Royal Hospital, Muscat, Oman.|Department of malaria, Ministry of Health, Muscat, Oman.
Said K
SK
Al-Mukhaini
Department of Infectious Diseases, The Royal Hospital, Muscat, Oman.|Department of malaria, Ministry of Health, Muscat, Oman.
Majed
M
Al-Zadjali
Department of Infectious Diseases, The Royal Hospital, Muscat, Oman.|Department of malaria, Ministry of Health, Muscat, Oman.
Seif S
SS
Al-Abri
Department of Infectious Diseases, The Royal Hospital, Muscat, Oman.|Department of malaria, Ministry of Health, Muscat, Oman.
Osama A M
OA
Ali
Entomology Department, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt.|Biodiversity Institute, University of Kansas, Lawrence, KS, 66045, USA.
Abdallah M
AM
Samy
Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, Medical Campus, University of Khartoum, Qassr Street, P.O. BOX 102, Khartoum, Sudan.
Muzamil Mahdi Abdel
MM
Hamid
Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, Medical Campus, University of Khartoum, Qassr Street, P.O. BOX 102, Khartoum, Sudan.
Musab M
MM
Ali Albsheer
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, Lyon, 69622, Villeurbane, France.|Institut of Parasitology and Medical Mycology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
Bruno
B
Simon
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, Lyon, 69622, Villeurbane, France.|Institut of Parasitology and Medical Mycology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
Anne-Lise
AL
Bienvenu
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.
Eskild
E
Petersen
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, Lyon, 69622, Villeurbane, France.|Institut of Parasitology and Medical Mycology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
Stéphane
S
Picot
D008435:Mauritania; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009850:Oman; D010966:Plasmodium vivax / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D013397:Sudan
D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C541684:Mdr1 protein, Plasmodium vivax
Apoptose; Drug resistance; Mauritania; Metacaspases; Oman; Plasmodium vivax; PvMCA1-cd; SNP; Sudan; pvmdr1 gene