Article
Public, Environmental & Occupational Health
Fengyue Hu, Qicheng Zou, Yinyue Li, Guoding Zhu, Huayun Zhou, Meihua Zhang, Fang Tian, Yaobao Liu, Feng Lu
Summary: This study demonstrates the feasibility of using the 23-SNP barcode to track P. falciparum, with results showing that most P. falciparum isolates originate from West Africa, while also revealing some isolates from Central Africa that originated in East Africa.
FRONTIERS IN PUBLIC HEALTH
(2021)
Article
Biochemistry & Molecular Biology
Russell P. Swift, Krithika Rajaram, Hans B. Liu, Sean T. Prigge
Summary: Malaria parasites have an essential organelle called the apicoplast, where metabolic pathways for various syntheses are housed. Studies show that isoprenoid synthesis appears to be the only essential function of the apicoplast in blood-stage parasites. Additionally, the enzyme DPCK responsible for coenzyme A synthesis is localized to the apicoplast and is essential for parasite survival.
Article
Multidisciplinary Sciences
Min Zhang, Chengqi Wang, Jenna Oberstaller, Phaedra Thomas, Thomas D. Otto, Debora Casandra, Sandhya Boyapalle, Swamy R. Adapa, Shulin Xu, Katrina Button-Simons, Matthew Mayho, Julian C. Rayner, Michael T. Ferdig, Rays H. Y. Jiang, John H. Adams
Summary: A large-scale forward genetic screen in malaria-causing Plasmodium falciparum identified over 200 mutants with differential responses to increased temperature, with implications for artemisinin sensitivity and oxidative stress. Critical processes associated with parasite tolerance to fever and artemisinin resistance include protein-folding, heat shock, and isoprenoid biosynthesis pathways derived from the parasite's algal endosymbiont ancestor genome. Parasites appear to exploit their innate febrile response mechanisms for artemisinin resistance, involving genes linked to the evolutionary origins of Plasmodium parasites.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
M. Andreina Pacheco, Randall E. Junge, Adithyan Menon, Jon McRoberts, Gediminas Valkiunas, Ananias A. Escalante
Summary: This study found six Plasmodium lineages in lemurs, indicating that lemurs play a role in the transmission of malaria parasites. The analysis of mitochondrial genomes and apicoplast loci suggests that the lemur Plasmodium clade shares a common ancestor with primate parasites from continental Africa, and the most lethal malaria parasite in humans, Plasmodium falciparum, may have originated from African apes. Furthermore, the study revealed a close phylogenetic relationship between lemurs and their parasites, with evidence of cospeciation, duplication, and host switching events.
MOLECULAR PHYLOGENETICS AND EVOLUTION
(2022)
Article
Microbiology
SooNee Tan, Devaraja G. Mudeppa, Sreekanth Kokkonda, John White, Rapatbhorn Patrapuvich, Pradipsinh K. Rathod
Summary: Research has shown that PfGyrA in malaria parasites is an apicoplast enzyme crucial for blood-stage parasites, potentially targeted by ciprofloxacin but not exclusively.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Jenni A. Hayward, F. Victor M. Makota, Daniela Cihalova, Rachel A. Leonard, Esther Rajendran, Soraya M. J. Zwahlen, Laura G. Shuttleworth, Ursula G. Wiedemann, Christina Spry, Kevin J. Saliba, Alexander G. Maier, Giel G. van Dooren
Summary: Apicomplexans, including the causative agents of malaria and toxoplasmosis, are widespread parasites that pose significant challenges for treatment. The mitochondrial electron transport chain (ETC) has been identified as a potential drug target in these parasites. Using a Seahorse XFe96 flux analyzer, researchers identified six chemically diverse inhibitors of the apicomplexan ETC, at least four of which also targeted the ETC of Plasmodium falciparum. These findings provide new insights into potential treatment options for drug resistant parasites. Evaluation: 10/10.
Article
Chemistry, Medicinal
Dyhia Amrane, Christophe-Sebastien Arnold, Sebastien Hutter, Julen Sanz-Serrano, Miguel Collia, Amaya Azqueta, Lucie Paloque, Anita Cohen, Nadia Amanzougaghene, Shahin Tajeri, Jean-Francois Franetich, Dominique Mazier, Francoise Benoit-Vical, Pierre Verhaeghe, Nadine Azas, Patrice Vanelle, Cyrille Botte, Nicolas Primas
Summary: A new compound (3i) with potential anti-malarial activity was discovered, showing potent activity targeting the apicoplast in malaria parasites and exhibiting selectivity. The compound showed good performance in genotoxicity tests and primarily relied on the CCl3 group for antiplasmodial activity.
Review
Microbiology
Rubayet Elahi, Sean Prigge
Summary: The apicoplast of Plasmodium falciparum is crucial for the synthesis of essential isoprenoid precursors and Coenzyme A (CoA), which are used both inside and outside the apicoplast. Recent reports have shed light on the roles of iron-sulfur cluster (FeS) cofactors in isoprenoid precursor synthesis and the utilization of these metabolites. This review discusses the recent insights and raises new questions pertaining to blood stage malaria parasites.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Review
Microbiology
Serena Shunmugam, Christophe-Sebastien Arnold, Sheena Dass, Nicholas J. Katris, Cyrille Y. Botte
Summary: This review discusses the role of lipids in Apicomplexa parasites and summarizes recent findings on the metabolic mechanisms involved in host nutrient adaptation.
Article
Chemistry, Medicinal
Eleonora Diamanti, Mostafa M. Hamed, Antoine Lacour, Patricia Bravo, Boris Illarionov, Markus Fischer, Matthias Rottmann, Matthias Witschel, Anna K. H. Hirsch
Summary: The MEP pathway enzymes are crucial for synthesizing isoprenoids and are potential drug targets. A high-throughput screening approach led to the discovery of a novel fragment hit against PfIspD, and a systematic SAR investigation identified a new compound for structure-guided optimization. A putative binding mode for the inhibitors was proposed using a homology model of PfIspD.
Article
Chemistry, Medicinal
Xu Wang, Rachel L. Edwards, Haley S. Ball, Kenneth M. Heidel, Robert C. Brothers, Claire Johnson, Amanda Haymond, Misgina Girma, Allyson Dailey, Jose Santinni Roma, Helena I. Boshoff, Damon M. Osbourn, Marvin J. Meyers, Robin D. Couch, Audrey R. Odom John, Cynthia S. Dowd
Summary: Malaria, a mosquito-borne disease caused by Plasmodium parasites, poses a significant threat to global public health with hundreds of thousands of deaths each year. The methyl erythritol phosphate (MEP) pathway, utilized by Plasmodium parasites and pathogenic bacteria, presents potential drug targets for treating malaria and bacterial infections.
ACS INFECTIOUS DISEASES
(2023)
Article
Parasitology
Marco Biddau, T. R. Santha Kumar, Philipp Henrich, Larissa M. Laine, Gavin J. Blackburn, Achuthanunni Chokkathukalam, Tao Li, Kim Lee Sim, Lewis King, Stephen L. Hoffman, Michael P. Barrett, Graham H. Coombs, Geoffrey I. McFadden, David A. Fidock, Sylke Mueller, Lilach Sheiner
Summary: The study highlights the importance of redox regulation in malaria parasites and suggests LipB as a potential target for the development of new transmission drugs. Deletion of lipB in Plasmodium falciparum impacts redox regulators expression, central carbon metabolism, and development in the mosquito, suggesting a role for lipB in these processes. Further research on LA biosynthesis is needed to better understand its role in asexual stages of malaria parasites.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Chemistry, Medicinal
Dyhia Amrane, Nicolas Primas, Christophe-Sebastien Arnold, Sebastien Hutter, Beatrice Louis, Julen Sanz-Serrano, Amaya Azqueta, Nadia Amanzougaghene, Shahin Tajeri, Dominique Mazier, Pierre Verhaeghe, Nadine Azas, Cyrille Botte, Patrice Vanelle
Summary: The discovery of a new drug target for antimalarials and the synthesis of compounds with antiplasmodial activity have been reported. One compound showed high selectivity and efficacy in in vitro experiments. Further biological investigations suggest that this compound may act by affecting the parasite's apicoplast.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Shivendra G. Tewari, Krithika Rajaram, Russell P. Swift, Jaques Reifman, Sean T. Prigge, Anders Wallqvist
Summary: The malaria parasite Plasmodium falciparum adapts to fosmidomycin treatment by increasing purine-based nucleotide synthesis and decreasing phosphatidylcholine synthesis. This metabolic adaptation allows the parasite to compensate for the loss of prenylation modifications and control RNA translation rate during the intraerythrocytic developmental cycle. Combination therapies targeting nucleotide synthesis or ribosomal biogenesis may be more effective than treating the parasite with fosmidomycin alone.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Microbiology
Camilla Pires, Jyotsna Chawla, Caroline Simmons, Justin Gibbons, John H. Adams
Summary: Fever is an important part of the human immune response to limit microbial growth, including the parasite Plasmodium falciparum that causes malaria. Recent research has revealed the complexity of the malaria parasite's heat-shock response, which helps alleviate cellular stress and maintain protein function. This review also discusses how the malaria parasite adapts its fever response to fight against artemisinin treatment and how this survival mechanism can contribute to the transmission of the parasite to mosquitoes.
CURRENT OPINION IN MICROBIOLOGY
(2023)
Article
Biochemical Research Methods
Jolyn E. Gisselberg, Lichao Zhang, Joshua E. Elias, Ellen Yeh
MOLECULAR & CELLULAR PROTEOMICS
(2017)
Article
Microbiology
Marta Walczak, Suresh M. Ganesan, Jacquin C. Niles, Ellen Yeh
Article
Biochemistry & Molecular Biology
Michael J. Boucher, Sreejoyee Ghosh, Lichao Zhang, Avantika Lal, Se Won Jang, An Ju, Shuying Zhang, Xinzi Wang, Stuart A. Ralph, James Zou, Joshua E. Elias, Ellen Yeh
Article
Microbiology
Ian T. Foe, Ouma Onguka, Katherine Amberg-Johnson, Rikki M. Garner, Neri Amara, Wandy Beatty, Ellen Yeh, Matthew Bogyo
Article
Microbiology
Katherine Amberg-Johnson, Ellen Yeh
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2019)
Correction
Microbiology
Ian T. Foe, Ouma Onguka, Katherine Amberg-Johnson, Rikki M. Garner, Neri Amara, Wandy Beatty, Ellen Yeh, Matthew Bogyo
Article
Microbiology
Michael J. Etoucher, Ellen Yeh
Article
Biochemistry & Molecular Biology
Yong Tang, Thomas R. Meister, Marta Walczak, Michael J. Pulkoski-Gross, Sanjay B. Hari, Robert T. Sauer, Katherine Amberg-Johnson, Ellen Yeh
Article
Microbiology
Michael J. Boucher, Ellen Yeh
Article
Infectious Diseases
Gretchen Ehrenkaufer, Pengyang Li, Erin E. Stebbins, Monica M. Kangussu-Marcolino, Anjan Debnath, Corin White, Matthew S. Moser, Joseph DeRisi, Jolyn Gisselberg, Ellen Yeh, Steven C. Wang, Ana Hervella Company, Ludovica Monti, Conor R. Caffrey, Christopher D. Huston, Bo Wang, Upinder Singh
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Microbiology
Thomas R. Meister, Yong Tang, Michael J. Pulkoski-Gross, Ellen Yeh
Article
Chemistry, Medicinal
Stephanie Kabeche, Jumpei Aida, Thamina Akther, Takashi Ichikawa, Atsuko Ochida, Michael J. Pulkoski-Gross, Mark Smith, Paul S. Humphries, Ellen Yeh
Summary: A series of novel thiazole-containing amides were synthesized and studied for their structure-activity relationship, leading to the identification of potent and selective PfFPPS/GGPPS inhibitors with good in vitro ADME profiles. The most promising candidate molecules were advanced to mouse in vivo PK studies, showing adequate free drug exposure for further investigation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Microbiology
Marta Walczak, Thomas R. Meister, Hoa Mai Nguyen, Yili Zhu, Sebastien Besteiro, Ellen Yeh
Summary: The most extensively studied role of Atg8 proteins is in autophagy. However, they also have other nonautophagic functions critical to cell function and disease pathogenesis that are understudied compared to their canonical role in autophagy. Atg8 family proteins are highly conserved eukaryotic proteins with diverse autophagy and nonautophagic functions in eukaryotes. The molecular changes that facilitated acquisition of divergent, nonautophagic functions of Atg8 are not well known.
Correction
Microbiology
Ian T. Foe, Ouma Onguka, Katherine Amberg-Johnson, Rikki M. Garner, Neri Amara, Wandy Beatty, Ellen Yeh, Matthew Bogyo
Article
Biochemistry & Molecular Biology
Jolyn E. Gisselberg, Zachary Herrera, Lindsey M. Orchard, Manuel Llinas, Ellen Yeh
CELL CHEMICAL BIOLOGY
(2018)