Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

• Published in: Scientific reports Vol. 6; no. 1; p. 33518
• Main Authors: Hart, Robert J., Cornillot, Emmanuel, Abraham, Amanah, Molina, Emily, Nation, Catherine S., Ben Mamoun, Choukri, Aly, Ahmed S. I.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.09.2016; Nature Publishing Group
• Subjects: 38/39; 42/109; 631/326/417/1716; 631/326/417/2550; Amino Acid Sequence; Animals; Anopheles; Anopheles - parasitology; Antimicrobial agents; Aquatic insects; Biosynthesis; Biosynthetic Pathways; Coenzyme A; Coenzyme A - biosynthesis; Conserved Sequence; Developmental stages; Disease transmission; Erythrocytes; Erythrocytes - parasitology; Female; Gene Deletion; Gene Expression Regulation; Gene regulation; Genes, Protozoan; Human health and pathology; Humanities and Social Sciences; Life Cycle Stages; Life cycles; Life Sciences; Malaria; Malaria - genetics; Malaria - parasitology; Mice, Inbred BALB C; Models, Biological; Mosquitoes; multidisciplinary; Oocysts; Oocysts - metabolism; Pantothenate kinase; Pantothenic acid; Parasites; Parasites - enzymology; Parasites - genetics; Parasites - growth & development; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases (Alcohol Group Acceptor) - chemistry; Phosphotransferases (Alcohol Group Acceptor) - genetics; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Phylogeny; Plasmodium; Plasmodium - enzymology; Plasmodium - genetics; Plasmodium - growth & development; Plasmodium falciparum; Protozoa; Protozoan Proteins; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Science; Sequence Analysis, DNA; Sexual stages; Sporozoites; Sporozoites - metabolism; Transcription; Transcription, Genetic; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep33518

The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B 5 ) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes ( PanK1 and PanK2 ) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii . We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.