Genetic analysis of glutathione synthetase of Plasmodium falciparum, a potential candidate for antimalarial drug development

Abstract

Glutathione synthetase (GS) is an enzyme involved in the synthesis of glutathione, a molecule protecting the parasite from heme-induced cell damage and potentially affecting antimalarial drug responses. Currently, the design of in silico assay for chemical screen is impeded due to the lack of complete gene sequences from endemic populations of malaria parasites. This study aimed to investigate the genetic diversity of the gs gene in P. falciparum populations in Thailand and worldwide. The catalog of the gs gene of P. falciparum was generated, consisting of sequences of 223 P. falciparum isolates from 15 countries. Population genetic analyses were conducted using the sequences of gs in the database to reveal the allelic and nucleotide diversity. In addition, the neutrality tests were performed to determine the evidence of natural selection. The analysis of the gs sequences in the database identified 55 unique haplotypes, characterized by 41 SNPs and 1 indel mutation. The most common gs haplotype was the gs1 which was found in all P. falciparum populations. Sequence analysis also revealed low genetic diversity at the gs locus, likely due to negative selection. In conclusion, the present study establishes the catalog of P. falciparum gs gene and provides basic genetic diversity information for antimalarial drug design and for monitoring the effects of antimalarial drugs on parasite populations.