Identification of an Anopheles Lineage-Specific Unique Heme Peroxidase HPX15: A Plausible Candidate for Arresting Malaria Parasite Development

Background: Human malaria parasite Plasmodium falciparum is transmitted by several species of Anopheles mosquito. The advancement of drug-resistant parasites and insecticide resistance in mosquito vectors are major hurdles in the malaria control. Alternatively, the manipulation of mosquito immunity is also an ideal way to block Plasmodium development inside the insect host. This approach demands the identification of key mosquito molecules that regulate anti-plasmodial immunity. Our previous findings revealed that the silencing of Anopheles gambiae heme peroxidase 15 (AgHPX15, AGAP013327) induced mosquito innate immunity and drastically suppressed the development of human and rodent malaria parasites. Further, we aim to characterize HPX15 orthologs in Indian malaria vectors and other worldwide-distributed anophelines to understand the novelty of this molecule as a plausible target to block Plasmodium development. Method: AgHPX15 orthologs were cloned from major Indian malaria vectors A. stephensi and A. culicifacies and their conserve domains were determined by CDD search tool. The sequence homology and phylogenetic relationship of these clones with other heme peroxidases was analysed using Mega5.2 software. Results and conclusion: We found that A. stephensi AsHPX15 and A. culicifacies AcHPX15 clones are close orthologs of A. gambiae AgHPX15. The phylogenetic relationship of these anopheline HPX15 with other animal and plant heme peroxidases revealed that they form a separate lineage-specific cluster and their orthologs are not found in human, nematodes or other related arthropods such as, Drosophila, Aedes and Culex mosquitoes. However, their putative orthologs are present in 16 other globally distributed anophelines and exhibit a highly conserved amino acids identity in the range of 70-99%. Based on these findings we propose that the anopheline-specific and evolutionary conserved heme peroxidase HPX15 may serve as a unique target for designing transmission-blocking strategies to block Plasmodium-mosquito cycle. These findings will generate new frontiers in the field of malaria research and disease control.