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10-Minute Presentation

Medical, Urban, and Veterinary Entomology

10-min: MUVE, Veterinary Entomology and Related Disease Vector Research

A leading drug candidate for a heritable metabolic disorder significantly reduces malaria parasite development in a globally invasive mosquito vector

Wednesday, November 13, 2024
10:18 AM – 10:30 AM MST
Location: Phoenix Convention Center, 221 C, PCC
Oral Presentation
Plasmodium parasites depend on their mosquito and vertebrate hosts for required nutrients to complete their life cycles. One essential nutrient, pantothenate, cannot be synthesized de novo by Plasmodium parasites and must be acquired from these hosts. Pantothenate is converted to coenzyme A in parasites and both hosts by the enzyme pantothenate kinase (PanK). Provisioning of a first-generation small molecule pantazine activator of mammalian PanK to the highly invasive global vector Anopheles stephensi revealed that conversion of pantothenate to coenzyme A in the mosquito can significantly reduce insect-stage malaria parasite development, presumably by starving parasites of this essential nutrient. We have recently tested a second-generation pantazine (PZ-3022) with improved stability and activity for infection-blocking activity in An. stephensi against the mouse parasite Plasmodium yoelii and the human parasite P. falciparum. Female An. stephensi were treated with a log dose range of PZ-3022 delivered via soaked cotton pads while a control group received water only. After three days, treatment and control groups were allowed to feed on mice infected with P. yoelii or on blood infected with P. falciparum using standard membrane feeding assays. At 10 d post-infection (PI) midguts were dissected and at 14 d PI salivary glands were dissected to determine the prevalence and intensity of oocyst and sporozoite infections, respectively. PZ-3022 treatment resulted in a significant reduction in oocyst and sporozoite infection intensities compared to control in both P. yoelii- and P. falciparum-infected mosquitoes. The findings suggest that PZ-3022 is a promising transmission-blocking candidate.