2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalaria
2013
Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission
Bobenchik AM, Witola WH, Augagneur Y, Lochlainn L, Garg A, Pachikara N, Choi JY, Zhao YO, Usmani-Brown S, Lee A, Adjalley SH, Samanta S, Fidock DA, Voelker DR, Fikrig E, Mamoun C. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 18262-18267. PMID: 24145416, PMCID: PMC3831454, DOI: 10.1073/pnas.1313965110.Peer-Reviewed Original ResearchConceptsAsexual replicationGametocyte developmentFunctional complementation assaysPhosphoethanolamine N-methyltransferaseHost serineComplementation assaysMalaria transmissionGenetic diversityPhosphoethanolamine methyltransferaseGametocyte differentiationFemale gametocytesSpecificity of inhibitionMetabolic analysisSynthesis of phosphatidylcholineGametocytogenesisChemical screeningPlasmodium speciesAnopheles mosquitoesN-methyltransferaseLow micromolar rangePathwayReplicationHuman erythrocytesParasitesGlobal burden