Journal
INFECTION AND IMMUNITY
Volume 91, Issue 7, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/iai.00167-23
Keywords
Malaria; Plasmodium; blood stages; gametes; exflagellation; mosquito transmission; amino acid decarboxylase; polyamine
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A frequent side effect of chemotherapy against malaria parasite blood infections is the induction of sexual blood stages, increasing the risk of future malaria transmissions. The polyamine biosynthesis pathway has been suggested as a target for anti-malarial drug development. This study focuses on the role of a bacterial-type amino acid decarboxylase (AAD) in the life cycle of the malaria model parasite Plasmodium yoelii. By targeting gene deletion, it was found that AAD is essential for the development of male gametes and transmission to mosquitoes.
A frequent side effect of chemotherapy against malaria parasite blood infections is a dramatic induction of the sexual blood stages, thereby enhancing the risk of future malaria transmissions. The polyamine biosynthesis pathway has been suggested as a candidate target for transmission-blocking anti-malarial drug development. Herein, we describe the role of a bacterial-type amino acid decarboxylase (AAD) in the life cycle of the malaria model parasite Plasmodium yoelii. Hallmarks of AAD include a conserved catalytic lysine residue and high-level homology to arginine/lysine/ornithine decarboxylases of pathogenic bacteria. By targeted gene deletion, we show that AAD plays an essential role in the exflagellation of microgametes, resulting in complete absence of sporozoites in the mosquito vector. These data highlight the central role of the biosysthesis of polyamines in the final steps of male gamete sexual development of the malaria parasite and, hence, onward transmission to mosquitoes.
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