title: Plasmodium falciparum and Plasmodium vivax specific lactate dehydrogenase: genetic polymorphism study from Indian isolates.
abstract: Control and eradication of malaria is hindered by the acquisition of drug resistance by Plasmodium species. This has necessitated a persistent search for novel drugs and more efficient targets. Plasmodium species specific lactate dehydrogenase is one of the potential therapeutic and diagnostic targets, because of its indispensable role in endoerythrocytic stage of the parasite. A target molecule that is highly conserved in the parasite population can be more effectively used in diagnostics and therapeutics, hence, in the present study polymorphism in PfLDH (Plasmodiumfalciparum specific LDH) and PvLDH (Plasmodiumvivax specific LDH) genes was analyzed using PCR-single strand confirmation polymorphism (PCR-SSCP) and sequencing. Forty-six P. falciparum and thirty-five P. vivax samples were screened from different states of India. Our findings have revealed presence of a single PfLDH genotype and six PvLDH genotypes among the studied samples. Interestingly, along with synonymous substitutions, nonsynonymous substitutions were reported to be present for the first time in the PvLDH genotypes. Further, through amino acid sequence alignment and homology modeling studies we observed that the catalytic residues were conserved in all PvLDH genotypes and the nonsynonymous substitutions have not altered the enzyme structure significantly. Evolutionary genetics studies have confirmed that PfLDH and PvLDH loci are under strong purifying selection. Phylogenetic analysis of the pLDH gene sequences revealed that P. falciparum compared to P. vivax, has recent origin. The study therefore supports PfLDH and PvLDH as suitable therapeutic and diagnostic targets as well as phylogenetic markers to understand the genealogy of malaria species.
authors: Department of Microbiology and Biotechnology Centre, The M.S. University of Baroda, Vadodara, Gujarat 390002, India.
authors: Priyadarshan
authors: P
authors: Keluskar
authors: National Institute of Malaria Research, Sector 8, Dwarka, Delhi 110077, India.
authors: Vineeta
authors: V
authors: Singh
authors: National Institute of Malaria Research, Sector 8, Dwarka, Delhi 110077, India.
authors: Purva
authors: P
authors: Gupta
authors: Department of Microbiology and Biotechnology Centre, The M.S. University of Baroda, Vadodara, Gujarat 390002, India. Electronic address: ingle05@yahoo.co.in.
authors: Sanjay
authors: S
authors: Ingle
mesh_terms: D000595:Amino Acid Sequence; D016054:DNA, Protozoan; D019143:Evolution, Molecular; D006801:Humans; D007194:India / Q000453:epidemiology; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D016054:DNA, Protozoan; D007770:L-Lactate Dehydrogenase
keywords: Genetic polymorphism; Lactate dehydrogenase; Malaria therapeutic diagnostic target; Plasmodium