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Plasmodium falciparum

  • Open Access
    The Key Glycolytic Enzyme Phosphofructokinase Is Involved in Resistance to Antiplasmodial Glycosides
    Research Article | Molecular Biology and Physiology
    The Key Glycolytic Enzyme Phosphofructokinase Is Involved in Resistance to Antiplasmodial Glycosides

    Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue, causing 405,000 deaths and 228 million cases in 2018. Understanding key metabolic processes in malaria parasites is critical to the development of new drugs to combat this major infectious disease. The Plasmodium glycolytic pathway is essential to the malaria parasite, providing energy for growth and replication and supplying...

    Gillian M. Fisher, Simon A. Cobbold, Andrew Jezewski, Emma F. Carpenter, Megan Arnold, Annie N. Cowell, Erick T. Tjhin, Kevin J. Saliba, Tina S. Skinner-Adams, Marcus C. S. Lee, Audrey Odom John, Elizabeth A. Winzeler, Malcolm J. McConville, Sally-Ann Poulsen, Katherine T. Andrews
  • Open Access
    Expansion of a Specific <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> PfMDR1 Haplotype in Southeast Asia with Increased Substrate Transport
    Research Article | Molecular Biology and Physiology
    Expansion of a Specific Plasmodium falciparum PfMDR1 Haplotype in Southeast Asia with Increased Substrate Transport

    Global efforts to eliminate malaria depend on the continued success of artemisinin-based combination therapies (ACTs) that target Plasmodium asexual blood-stage parasites. Resistance to ACTs, however, has emerged, creating the need to define the underlying mechanisms. Mutations in the P. falciparum multidrug resistance protein 1 (PfMDR1) transporter...

    Carla Calçada, Miguel Silva, Vitória Baptista, Vandana Thathy, Rita Silva-Pedrosa, Diana Granja, Pedro Eduardo Ferreira, José Pedro Gil, David A. Fidock, Maria Isabel Veiga
  • Open Access
    <span class="named-content genus-species" id="named-content-1">Plasmodium berghei</span> K13 Mutations Mediate <em>In Vivo</em> Artemisinin Resistance That Is Reversed by Proteasome Inhibition
    Editor's Pick Research Article | Host-Microbe Biology
    Plasmodium berghei K13 Mutations Mediate In Vivo Artemisinin Resistance That Is Reversed by Proteasome Inhibition

    Recent successes in malaria control have been seriously threatened by the emergence of Plasmodium falciparum parasite resistance to the frontline artemisinin drugs in Southeast Asia. P. falciparum artemisinin resistance is associated with mutations in the parasite K13 protein, which associates with...

    Nelson V. Simwela, Barbara H. Stokes, Dana Aghabi, Matt Bogyo, David A. Fidock, Andrew P. Waters
  • Open Access
    The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins
    Research Article | Molecular Biology and Physiology
    The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins

    The phylum of Apicomplexa groups medically relevant parasites such as those responsible for malaria and toxoplasmosis. As members of the Alveolata superphylum, these protozoans possess specialized organelles in addition to those found in all members of the eukaryotic kingdom. Vesicular trafficking is the major route of communication between membranous organelles. Neither the molecular mechanism that allows communication between...

    Hugo Bisio, Rouaa Ben Chaabene, Ricarda Sabitzki, Bohumil Maco, Jean Baptiste Marq, Tim-Wolf Gilberger, Tobias Spielmann, Dominique Soldati-Favre
  • Open Access
    <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Apicomplexan-Specific Glucosamine-6-Phosphate <em>N</em>-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage Development
    Research Article | Molecular Biology and Physiology
    Plasmodium falciparum Apicomplexan-Specific Glucosamine-6-Phosphate N-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage Development

    Apicomplexan parasites cause a major burden on global health and economy. The absence of treatments, the emergence of resistances against available therapies, and the parasite’s ability to manipulate host cells and evade immune systems highlight the urgent need to characterize new drug targets to treat infections caused by these parasites. We demonstrate that glucosamine-6-phosphate N-acetyltransferase (GNA1), required for the...

    Jordi Chi, Marta Cova, Matilde de las Rivas, Ana Medina, Rafael Junqueira Borges, Pablo Leivar, Antoni Planas, Isabel Usón, Ramón Hurtado-Guerrero, Luis Izquierdo
  • Open Access
    The Structure of the Cysteine-Rich Domain of <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> P113 Identifies the Location of the RH5 Binding Site
    Research Article | Host-Microbe Biology
    The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site

    Malaria is a deadly infectious disease primarily caused by the parasite Plasmodium falciparum. It remains a major global health problem, and there is no highly effective vaccine. A parasite protein called RH5 is centrally involved in the invasion of host red blood cells, making it—and the other parasite proteins it interacts with—promising vaccine targets. We recently...

    Ivan Campeotto, Francis Galaway, Shahid Mehmood, Lea K. Barfod, Doris Quinkert, Vinayaka Kotraiah, Timothy W. Phares, Katherine E. Wright, Ambrosius P. Snijders, Simon J. Draper, Matthew K. Higgins, Gavin J. Wright
  • Open Access
    Live-Cell FRET Reveals that Malaria Nutrient Channel Proteins CLAG3 and RhopH2 Remain Associated throughout Their Tortuous Trafficking
    Research Article | Molecular Biology and Physiology
    Live-Cell FRET Reveals that Malaria Nutrient Channel Proteins CLAG3 and RhopH2 Remain Associated throughout Their Tortuous Trafficking

    Malaria parasites grow within circulating red blood cells and uptake nutrients through a pore on their host membrane. Here, we used gene editing to tag CLAG3 and RhopH2, two proteins linked to the nutrient pore, with fluorescent markers and tracked these proteins in living infected cells. After their synthesis in mature parasites, imaging showed that both proteins are packaged into membrane-bound rhoptries. When parasites ruptured their...

    Moaz Ahmad, Javier Manzella-Lapeira, Gagandeep Saggu, Daisuke Ito, Joseph A. Brzostowski, Sanjay A. Desai
  • Open Access
    The <em>Plasmodium falciparum</em> Artemisinin Susceptibility-Associated AP-2 Adaptin μ Subunit is Clathrin Independent and Essential for Schizont Maturation
    Research Article | Molecular Biology and Physiology
    The Plasmodium falciparum Artemisinin Susceptibility-Associated AP-2 Adaptin μ Subunit is Clathrin Independent and Essential for Schizont Maturation

    We examine in detail the AP-2 adaptin complex from the malaria parasite Plasmodium falciparum. In most studied organisms, AP-2 is involved in bringing material into the cell from outside, a process called endocytosis. Previous work shows that changes to the μ subunit of AP-2 can contribute to drug resistance. Our experiments show that AP-2 is essential for parasite...

    Ryan C. Henrici, Rachel L. Edwards, Martin Zoltner, Donelly A. van Schalkwyk, Melissa N. Hart, Franziska Mohring, Robert W. Moon, Stephanie D. Nofal, Avnish Patel, Christian Flueck, David A. Baker, Audrey R. Odom John, Mark C. Field, Colin J. Sutherland
  • Open Access
    Role of <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Kelch 13 Protein Mutations in <span class="named-content genus-species" id="named-content-2">P. falciparum</span> Populations from Northeastern Myanmar in Mediating Artemisinin Resistance
    Research Article | Host-Microbe Biology
    Role of Plasmodium falciparum Kelch 13 Protein Mutations in P. falciparum Populations from Northeastern Myanmar in Mediating Artemisinin Resistance

    Artemisinin resistance has emerged in Southeast Asia, endangering the substantial progress in malaria elimination worldwide. It is associated with mutations in the PfK13 protein, but how PfK13 mediates artemisinin resistance is not completely understood. Here we used a new antibody against PfK13 to show that the PfK13 protein is expressed in all stages of the asexual intraerythrocytic cycle as well as in gametocytes and is partially...

    Faiza Amber Siddiqui, Rachasak Boonhok, Mynthia Cabrera, Huguette Gaelle Ngassa Mbenda, Meilian Wang, Hui Min, Xiaoying Liang, Junling Qin, Xiaotong Zhu, Jun Miao, Yaming Cao, Liwang Cui
  • Open Access
    <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation
    Research Article | Therapeutics and Prevention
    Plasmodium falciparum Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation

    Benzoxaboroles are under study as potential new drugs to treat malaria. One benzoxaborole, AN13762, has potent activity and promising features, but its mechanisms of action and resistance are unknown. To gain insights into these mechanisms, we cultured malaria parasites with nonlethal concentrations of AN13762 and generated parasites with varied levels of resistance. Parasites with low-level resistance had mutations in PfPARE, which...

    Kirthana M. V. Sindhe, Wesley Wu, Jenny Legac, Yong-Kang Zhang, Eric E. Easom, Roland A. Cooper, Jacob J. Plattner, Yvonne R. Freund, Joseph L. DeRisi, Philip J. Rosenthal

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