Malaria: Targets and Drugs for All Stages

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Posted on May 7, 2013
Image Credit: Delves M, Plouffe D, Scheurer C, Meister S, et al.

Image Credit: Delves M, Plouffe D, Scheurer C, Meister S, et al.

Malaria is an ancient enemy. Its treatments predate modern drug discovery, most notably the use of the Qinghao plant in ancient China (2nd century BC to 340 CE) and Peruvian bark in the early 17th century, the medicines from which are now known to be artemisinin and quinine respectively. Calls for the eradication of malaria have brought renewed focus on tools to control malaria.  Yet, although disease burdens have been lowered in the last five years, malaria remains endemic in over 100 countries and, with an estimated seven hundred thousand deaths in 2010, is still a leading cause of mortality and morbidity worldwide.

Drug research in malaria often focuses on blood stage parasites because they are responsible for the symptoms of the disease and are easier to manipulate in the laboratory.   The assembled PLOS Collection describes multiple parasite and host processes engaged in infection in blood, the blocking of which could stop human illness. However, control and eradication of malaria will also require the development of drugs against stages responsible for mosquito transmission and those that remain latent in the liver, also summarized in the collection. Although these selected papers represent significant research at the highest levels, they are only a fraction of the malaria drug discovery literature.

Despite research, a significant historical hurdle was the market failure of the pharmaceutical industry to invest in the discovery and development of new antimalarials.  Thus new partnerships have arisen that bring together academic and pharmaceutical work.  For example, the not-for-profit product development partnership Medicines for Malaria Venture (MMV) was established in 1999 to discover, develop and deliver new antimalarials in collaboration with both the public and private sector.

They are joined by the Bill and Melinda Gates Foundation , multiple agencies including the National Institutes of Health , the Wellcome Trust, Medical Research Council and others. Never before have philanthropic, public and large Pharma resources been better integrated for antimalarials, progressing research in early stages to testing drugs in humans, subsequent registration and delivery to patients.

Unfortunately, resistance frequently arises to any widely-used single drug. In the last five years, strong gains were made through combinations such as artemisinin-combination therapies (ACTs) where artemisinins were combined with a partner to which resistance had emerged.  But now there are signs of resistance to artemisinins, the spread of which would wipe out recent gains.

However in HIV, three drug combinations and first, second and third line combinations are being used to win the fight against AIDS. Malaria has proved a challenge, but there is hope; compared to viruses, the parasites’ mutation rate is lower and disease management is relatively straightforward.  Thus expanding the existing robust pipeline to create and enlarge the range of combination therapies against blood stage and other parasite stages can secure the therapies needed to achieve a long awaited public health triumph.

We dedicate this article to the late Dr. Ian Bathurst, a founding MMV program officer, for his key guidance.


Malaria: Targets and Drugs for All Stages 

This collection highlights PLOS (Pathogens, NTDs and Medicine) authors contribution to basic drug discovery research. The articles are organized into sections as follows: overview, targeting the parasite (blood stage asexual and sexual stages; liver and insect stages) and targeting the host (both mammalian and insect vector).


The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites Michael Delves, David Plouffe, Christian Scheurer, Stephan Meister, Sergio Wittlin, Elizabeth A. Winzeler, Robert E. Sinden, Didier Leroy Research Article | published 21 Feb 2012 | PLOS Medicine 10.1371/journal.pmed.1001169

1.Targeting the parasite.

1.1 Blood stages
1.1. A.Invasion

Structural and Functional Insights into the Malaria Parasite Moving Junction Complex Brigitte Vulliez-Le Normand, Michelle L. Tonkin, Mauld H. Lamarque, Susann Langer, Sylviane Hoos, Magali Roques, Frederick A. Saul, Bart W. Faber, Graham A. Bentley, Martin J. Boulanger, Maryse Lebrun Research Article | published 21 Jun 2012 | PLOS Pathogens 10.1371/journal.ppat.1002755

Juxtamembrane Shedding of Plasmodium falciparum AMA1 Is Sequence Independent and Essential, and Helps Evade Invasion-Inhibitory Antibodies Anna Olivieri, Christine R. Collins, Fiona Hackett, Chrislaine Withers-Martinez, Joshua Marshall, Helen R. Flynn, J. Mark Skehel, Michael J. Blackman Research Article | published 15 Dec 2011 | PLOS Pathogens 10.1371/journal.ppat.1002448  

Plasmodium Protease ROM1 Is Important for Proper Formation of the Parasitophorous Vacuole Iset Medina Vera, Wandy L. Beatty, Photini Sinnis, Kami Kim Research Article | published 01 Sep 2011 | PLOS Pathogens10.1371/journal.ppat.1002197

Distinct External Signals Trigger Sequential Release of Apical Organelles during Erythrocyte Invasion by Malaria Parasites Shailja Singh, M. Mahmood Alam, Ipsita Pal-Bhowmick, Joseph A. Brzostowski, Chetan E. Chitnis Research Article | published 05 Feb 2010 | PLOS Pathogens 10.1371/journal.ppat.1000746

Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite Kerstin Leykauf, Moritz Treeck, Paul R. Gilson, Thomas Nebl, Thomas Braulke, Alan F. Cowman, Tim W. Gilberger, Brendan S. Crabb Research Article | published 03 Jun 2010 | PLOS Pathogens 10.1371/journal.ppat.1000941

A Cyclic GMP Signalling Module That Regulates Gliding Motility in a Malaria Parasite Robert W. Moon, Cathy J. Taylor, Claudia Bex, Rebecca Schepers, David Goulding, Chris J. Janse, Andrew P. Waters, David A. Baker, Oliver Billker Research Article | published 25 Sep 2009 | PLOS Pathogens 10.1371/journal.ppat.1000599

Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process Moritz Treeck, Sonja Zacherl, Susann Herrmann, Ana Cabrera, Maya Kono, Nicole S. Struck, Klemens Engelberg, Silvia Haase, Friedrich Frischknecht, Kota Miura, Tobias Spielmann, Tim W. Gilberger Research Article | published 06 Mar 2009 | PLOS Pathogens 10.1371/journal.ppat.1000322

Epigenetic Silencing of Plasmodium falciparum Genes Linked to Erythrocyte Invasion Alfred Cortés, Celine Carret, Osamu Kaneko, Brian Y. S. Yim Lim, Alasdair Ivens, Anthony A Holder Research Article | published 03 Aug 2007 | PLOS Pathogens 10.1371/journal.ppat.0030107

Falstatin, a Cysteine Protease Inhibitor of Plasmodium falciparum, Facilitates Erythrocyte Invasion Kailash C Pandey, Naresh Singh, Shirin Arastu-Kapur, Matthew Bogyo, Philip J Rosenthal Research Article | published 03 Nov 2006 | PLOS Pathogens 10.1371/journal.ppat.0020117

Two Plasmodium Rhomboid Proteases Preferentially Cleave Different Adhesins Implicated in All Invasive Stages of Malaria Rosanna P Baker, Ruvini Wijetilaka, Sinisa Urban Research Article | published 13 Oct 2006 | PLOS Pathogens 10.1371/journal.ppat.0020113

Molecular Identification of a Malaria Merozoite Surface Sheddase Philippa K Harris, Sharon Yeoh, Anton R Dluzewski, Rebecca A O’Donnell, Chrislaine Withers-Martinez, Fiona Hackett, Lawrence H Bannister, Graham H Mitchell, Michael J Blackman Research Article | published 25 Nov 2005 | PLOS Pathogens 10.1371/journal.ppat.0010029

1.1.B.Growth/replication within infected erythrocyte.

Dynamic Epigenetic Regulation of Gene Expression during the Life Cycle of Malaria Parasite Plasmodium falciparum Archna P. Gupta, Wai Hoe Chin, Lei Zhu, Sachel Mok, Yen-Hoon Luah, Eng-How Lim, Zbynek Bozdech Research Article | published 28 Feb 2013 | PLOS Pathogens 10.1371/journal.ppat.1003170

An Analytical Method for Assessing Stage-Specific Drug Activity in Plasmodium vivax Malaria: Implications for Ex Vivo Drug Susceptibility Testing Douglas H. Kerlin, Kane Boyce, Jutta Marfurt, Julie A. Simpson, Enny Kenangalem, Qin Cheng, Ric N. Price, Michelle L. Gatton Research Article | published 07 Aug 2012 | PLOS Neglected Tropical Diseases10.1371/journal.pntd.0001772

Selective Inhibitors of Protozoan Protein N-myristoyltransferases as Starting Points for Tropical Disease Medicinal Chemistry Programs Andrew S. Bell, James E. Mills, Gareth P. Williams, James A. Brannigan, Anthony J. Wilkinson, Tanya Parkinson, Robin J. Leatherbarrow, Edward W. Tate, Anthony A. Holder, Deborah F. Smith Research Article | published 24 Apr 2012 | PLOS Neglected Tropical Diseases10.1371/journal.pntd.0001625

Integrated Dataset of Screening Hits against Multiple Neglected Disease Pathogens Solomon Nwaka, Dominique Besson, Bernadette Ramirez, Louis Maes, An Matheeussen, Quentin Bickle, Nuha R. Mansour, Fouad Yousif, Simon Townson, Suzanne Gokool, Fidelis Cho-Ngwa, Moses Samje, Shailja Misra-Bhattacharya, P. K. Murthy, Foluke Fakorede, Jean-Marc Paris, Clive Yeates, Robert Ridley, Wesley C. Van Voorhis, Timothy Geary Research Article | published 20 Dec 2011 | PLOS Neglected Tropical Diseases 10.1371/journal.pntd.0001412

Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads Kenny K. H. Ang, Joseline Ratnam, Jiri Gut, Jennifer Legac, Elizabeth Hansell, Zachary B. Mackey, Katarzyna M. Skrzypczynska, Anjan Debnath, Juan C. Engel, Philip J. Rosenthal, James H. McKerrow, Michelle R. Arkin, Adam R. Renslo Research Article | published 03 May 2011 | PLOS Neglected Tropical Diseases 10.1371/journal.pntd.0001023

Identification of a Mutant PfCRT-Mediated Chloroquine Tolerance Phenotype in Plasmodium falciparum Stephanie G. Valderramos, Juan-Carlos Valderramos, Lise Musset, Lisa A. Purcell, Odile Mercereau-Puijalon, Eric Legrand, David A. Fidock Research Article | published 13 May 2010 | PLOS Pathogens 10.1371/journal.ppat.1000887

Origin and Evolution of Sulfadoxine Resistant Plasmodium falciparum Sumiti Vinayak, Md Tauqeer Alam, Tonya Mixson-Hayden, Andrea M. McCollum, Rithy Sem, Naman K. Shah, Pharath Lim, Sinuon Muth, William O. Rogers, Thierry Fandeur, John W. Barnwell, Ananias A. Escalante, Chansuda Wongsrichanalai, Frederick Ariey, Steven R. Meshnick, Venkatachalam Udhayakumar Research Article | published 26 Mar 2010 | PLOS Pathogens 10.1371/journal.ppat.1000830

Histone Deacetylases Play a Major Role in the Transcriptional Regulation of the Plasmodium falciparum Life Cycle Balbir K. Chaal, Archna P. Gupta, Brigitta D. Wastuwidyaningtyas, Yen-Hoon Luah, Zbynek Bozdech Research Article | published 22 Jan 2010 | PLOS Pathogens 10.1371/journal.ppat.1000737

Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates Margaret J. Mackinnon, Jinguang Li, Sachel Mok, Moses M. Kortok, Kevin Marsh, Peter R. Preiser, Zbynek Bozdech Research Article | published 30 Oct 2009 | PLOS Pathogen. 10.1371/journal.ppat.1000644

Advancing Drug Innovation for Neglected Diseases—Criteria for Lead Progression Solomon Nwaka, Bernadette Ramirez, Reto Brun, Louis Maes, Frank Douglas, Robert Ridley Review | published 25 Aug 2009 | PLOS Neglected Tropical Diseases10.1371/journal.pntd.0000440

The Glutathione Biosynthetic Pathway of Plasmodium Is Essential for Mosquito Transmission Joel Vega-Rodríguez, Blandine Franke-Fayard, Rhoel R. Dinglasan, Chris J. Janse, Rebecca Pastrana-Mena, Andrew P. Waters, Isabelle Coppens, José F. Rodríguez-Orengo, Marcelo Jacobs-Lorena, Adelfa E. Serrano Research Article | published 20 Feb 2009 | PLOS Pathogens 10.1371/journal.ppat.1000302

Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis  Prakash Srinivasan, Isabelle Coppens, Marcelo Jacobs-Lorena Research Article | published 16 Jan 2009 | PLOS Pathogens 10.1371/journal.ppat.1000262

A Genetically Hard-Wired Metabolic Transcriptome in Plasmodium falciparum Fails to Mount Protective Responses to Lethal Antifolates. Karthikeyan Ganesan, Napawan Ponmee, Lei Jiang, Joseph W. Fowble, John White, Sumalee Kamchonwongpaisan, Yongyuth Yuthavong, Prapon Wilairat, Pradipsinh K. Rathod Research Article | published 21 Nov 2008 | PLOS Pathogens 10.1371/journal.ppat.1000214

An Erythrocyte Vesicle Protein Exported by the Malaria Parasite Promotes Tubovesicular Lipid Import from the Host Cell Surface Pamela A. Tamez, Souvik Bhattacharjee, Christiaan van Ooij, N. Luisa Hiller, Manuel Llinás, Bharath Balu, John H. Adams, Kasturi Haldar Research Article | published 08 Aug 2008 | PLOS Pathogens 10.1371/journal.ppat.1000118

The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection Christiaan van Ooij, Pamela Tamez, Souvik Bhattacharjee, N. Luisa Hiller, Travis Harrison, Konstantinos Liolios, Taco Kooij, Jai Ramesar, Bharath Balu, John Adams, Andy Waters, Chris Janse, Kasturi Haldar Research Article | published 13 Jun 2008 | PLOS Pathogens 10.1371/journal.ppat.1000084

HDP—A Novel Heme Detoxification Protein from the Malaria Parasite Dewal Jani, Rana Nagarkatti, Wandy Beatty, Ross Angel, Carla Slebodnick, John Andersen, Sanjai Kumar, Dharmendar Rathore Research Article | published 25 Apr 2008 | PLOS Pathogens 10.1371/journal.ppat.1000053

Plasmodium falciparum Regulatory Subunit of cAMP-Dependent PKA and Anion Channel Conductance Anaïs Merckx, Marie-Paule Nivez, Guillaume Bouyer, Pietro Alano, Gordon Langsley, Kirk Deitsch, Serge Thomas, Christian Doerig, Stéphane Egée Research Article | published 01 Feb 2008 | PLOS Pathogens 10.1371/journal.ppat.0040019

Compartmentation of Redox Metabolism in Malaria Parasites Sebastian Kehr, Nicole Sturm, Stefan Rahlfs, Jude M. Przyborski, Katja Becker Research Article | published 23 Dec 2010 | PLOS Pathogens 10.1371/journal.ppat.1001242

Microfluidic Modeling of Cell−Cell Interactions in Malaria Pathogenesis Meher Antia, Thurston Herricks, Pradipsinh K Rathod  Research Article | published 20 Jul 2007 | PLOS Pathogens 10.1371/journal.ppat.0030099

Release of Sequestered Malaria Parasites upon Injection of a Glycosaminoglycan Anna M Vogt, Fredrik Pettersson, Kirsten Moll, Cathrine Jonsson, Johan Normark, Ulf Ribacke, Thomas G Egwang, Hans-Peter Ekre, Dorothe Spillmann, Qijun Chen, Mats Wahlgren Research Article | published 29 Sep 2006 | PLOS Pathogens 10.1371/journal.ppat.0020100

A Systematic Map of Genetic Variation in Plasmodium falciparum Claire Kidgell, Sarah K Volkman, Johanna Daily, Justin O Borevitz, David Plouffe, Yingyao Zhou, Jeffrey R Johnson, Karine G. Le Roch, Ousmane Sarr, Omar Ndir, Soulyemane Mboup, Serge Batalov, Dyann F Wirth, Elizabeth A Winzeler Research Article | published 23 Jun 2006 | PLOS Pathogens 10.1371/journal.ppat.0020057

1.1.C. Sexual stages

The Plasmodium berghei Ca2+/H+ Exchanger, PbCAX, Is Essential for Tolerance to Environmental Ca2+ during Sexual Development David S. Guttery, Jon K. Pittman, Karine Frénal, Benoit Poulin, Leon R. McFarlane, Ksenija Slavic, Sally P. Wheatley, Dominique Soldati-Favre, Sanjeev Krishna, Rita Tewari, Henry M. Staines Research Article | published 28 Feb 2013 | PLOS Pathogens 10.1371/journal.ppat.1003191

Plasmodium falciparum Gametocyte Development 1 (Pfgdv1) and Gametocytogenesis Early Gene Identification and Commitment to Sexual Development Saliha Eksi, Belinda J. Morahan, Yoseph Haile, Tetsuya Furuya, Hongying Jiang, Omar Ali, Huichun Xu, Kirakorn Kiattibutr, Amreena Suri, Beata Czesny, Adebowale Adeyemo, Timothy G. Myers, Jetsumon Sattabongkot, Xin-zhuan Su, Kim C. Williamson Research Article | published 18 Oct 2012 | PLOS Pathogens 10.1371/journal.ppat.1002964

A Putative Homologue of CDC20/CDH1 in the Malaria Parasite Is Essential for Male Gamete Development David S. Guttery, David J. P. Ferguson, Benoit Poulin, Zhengyao Xu, Ursula Straschil, Onny Klop, Lev Solyakov, Sara M. Sandrini, Declan Brady, Conrad A. Nieduszynski, Chris J. Janse, Anthony A. Holder, Andrew B. Tobin, Rita Tewari Research Article | published 23 Feb 2012 | PLOS Pathogens 10.1371/journal.ppat.1002554

Identification of Attractive Drug Targets in Neglected-Disease Pathogens Using an In Silico Approach Gregory J. Crowther, Dhanasekaran Shanmugam, Santiago J. Carmona, Maria A. Doyle, Christiane Hertz-Fowler, Matthew Berriman, Solomon Nwaka, Stuart A. Ralph, David S. Roos, Wesley C. Van Voorhis, Fernán Agüero Research Article | published 24 Aug 2010 | PLOS Neglected Tropical Diseases 10.1371/journal.pntd.0000804

1.1.D.All blood (asexual and sexual) stages

Plasmodium knowlesi: Reservoir Hosts and Tracking the Emergence in Humans and Macaques Kim-Sung Lee, Paul C. S. Divis, Siti Khatijah Zakaria, Asmad Matusop, Roynston A. Julin, David J. Conway, Janet Cox-Singh, Balbir SinghResearch Article | published 07 Apr 2011 | PLOS Pathogens10.1371/journal.ppat.1002015

A Systems-Based Analysis of Plasmodium vivax Lifecycle Transcription from Human to Mosquito Scott J. Westenberger, Colleen M. McClean, Rana Chattopadhyay, Neekesh V. Dharia, Jane M. Carlton, John W. Barnwell, William E. Collins, Stephen L. Hoffman, Yingyao Zhou, Joseph M. Vinetz, Elizabeth A. Winzeler Research Article | published 06 Apr 2010 | PLOS Neglected Tropical Diseases 10.1371/journal.pntd.0000653

1.2 Liver stages

The Next Opportunity in Anti-Malaria Drug Discovery: The Liver Stage Emily R. Derbyshire, Maria M. Mota, Jon Clardy Opinion | published 22 Sep 2011 | PLOS Pathogens 10.1371/journal.ppat.1002178

Hostile Takeover by Plasmodium: Reorganization of Parasite and Host Cell Membranes during Liver Stage Egress  Stefanie Graewe, Kathleen E. Rankin, Christine Lehmann, Christina Deschermeier, Leonie Hecht, Ulrike Froehlke, Rebecca R. Stanway, Volker Heussler Research Article | published 01 Sep 2011 | PLOS Pathogens 10.1371/journal.ppat.1002224

1.3.Insect stages

A Unique Protein Phosphatase with Kelch-Like Domains (PPKL) in Plasmodium Modulates Ookinete Differentiation, Motility and Invasion David S. Guttery, Benoit Poulin, David J. P. Ferguson, Balázs Szöőr, Bill Wickstead, Paula L. Carroll, Chandra Ramakrishnan, Declan Brady, Eva-Maria Patzewitz, Ursula Straschil, Lev Solyakov, Judith L. Green, Robert E. Sinden, Andrew B. Tobin, Anthony A. Holder, Rita Tewari Research Article | published 20 Sep 2012 | PLOS Pathogens 10.1371/journal.ppat.1002948

Shedding of TRAP by a Rhomboid Protease from the Malaria Sporozoite Surface Is Essential for Gliding Motility and Sporozoite Infectivity Ijeoma Ejigiri, Daniel R. T. Ragheb, Paco Pino, Alida Coppi, Brandy Lee Bennett, Dominique Soldati-Favre, Photini Sinnis Research Article | published 26 Jul 2012 | PLOS Pathogens 10.1371/journal.ppat.1002725

Sexual Development in Plasmodium: Lessons from Functional Analyses David S. Guttery, Anthony A. Holder, Rita Tewari Pearls | published 19 Jan 2012 | PLOS Pathogens 10.1371/journal.ppat.1002404

Exoerythrocytic Plasmodium Parasites Secrete a Cysteine Protease Inhibitor Involved in Sporozoite Invasion and Capable of Blocking Cell Death of Host Hepatocytes Annika Rennenberg, Christine Lehmann, Anna Heitmann, Tina Witt, Guido Hansen, Krishna Nagarajan, Christina Deschermeier, Vito Turk, Rolf Hilgenfeld, Volker T. Heussler Research Article | published 26 Mar 2010 | PLOS Pathogens 10.1371/journal.ppat.1000825

Universal Features of Post-Transcriptional Gene Regulation Are Critical for Plasmodium Zygote Development Gunnar R. Mair, Edwin Lasonder, Lindsey S. Garver, Blandine M. D. Franke-Fayard, Céline K. Carret, Joop C. A. G. Wiegant, Roeland W. Dirks, George Dimopoulos, Chris J. Janse, Andrew P. Waters Research Article | published 12 Feb 2010 | PLOS Pathogens 10.1371/journal.ppat.1000767

Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity Edwin Lasonder, Chris J. Janse, Geert-Jan van Gemert, Gunnar R. Mair, Adriaan M. W. Vermunt, Bruno G. Douradinha, Vera van Noort, Martijn A. Huynen, Adrian J. F. Luty, Hans Kroeze, Shahid M. Khan, Robert W. Sauerwein, Andrew P. Waters, Matthias Mann, Hendrik G. Stunnenberg Research Article | published 31 Oct 2008 | PLOS Pathogens 10.1371/journal.ppat.1000195

Exit of Plasmodium Sporozoites from Oocysts Is an Active Process That Involves the Circumsporozoite Protein Qian Wang, Hisashi Fujioka, Victor Nussenzweig Research Article | published 30 Sep 2005 | PLOS Pathogens 10.1371/journal.ppat.0010009

2.0 Targeting the host.

2.1 Human/mammal

Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria Patricia A. Reis, Vanessa Estato, Tathiany I. da Silva, Joana C. d’Avila, Luciana D. Siqueira, Edson F. Assis, Patricia T. Bozza, Fernando A. Bozza, Eduardo V. Tibiriça, Guy A. Zimmerman, Hugo C. Castro-Faria-Neto Research Article | published 27 Dec 2012 | PLOS Pathogens 10.1371/journal.ppat.1003099

Cognitive Dysfunction Is Sustained after Rescue Therapy in Experimental Cerebral Malaria, and Is Reduced by Additive Antioxidant Therapy Patricia A. Reis, Clarissa M. Comim, Fernanda Hermani, Bruno Silva, Tatiana Barichello, Aline C. Portella, Flavia C. A. Gomes, Ive M. Sab, Valber S. Frutuoso, Marcus F. Oliveira, Patricia T. Bozza, Fernando A. Bozza, Felipe Dal-Pizzol, Guy A. Zimmerman, João Quevedo, Hugo C. Castro-Faria-Neto Research Article | published 24 Jun 2010 | PLOS Pathogens 10.1371/journal.ppat.1000963

Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases Marina Tiemi Shio, Stephanie C. Eisenbarth, Myriam Savaria, Adrien F. Vinet, Marie-Josée Bellemare, Kenneth W. Harder, Fayyaz S. Sutterwala, D. Scott Bohle, Albert Descoteaux, Richard A. Flavell, Martin Olivier Research Article | published 21 Aug 2009 | PLOS Pathogens 10.1371/journal.ppat.1000559

Kinome-Wide RNAi Screen Implicates at Least 5 Host Hepatocyte Kinases in Plasmodium Sporozoite Infection Miguel Prudêncio, Cristina D. Rodrigues, Michael Hannus, Cécilie Martin, Eliana Real, Lígia A. Gonçalves, Céline Carret, Robert Dorkin, Ingo Röhl, Kerstin Jahn-Hoffmann, Adrian J. F. Luty, Robert Sauerwein, Christophe J. Echeverri, Maria M. Mota Research Article | published 07 Nov 2008 | PLOS Pathogens. 10.1371/journal.ppat.1000201

Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy Sean Murphy Travis Harrison, Heidi E Hamm, Jon W Lomasney, Narla Mohandas, Kasturi Haldar Research Article | published 26 Dec 2006 | PLOS Medicine 10.1371/journal.pmed.0030528

Targeting of Endothelial Activation in Cerebral Malaria Synopsis | published 23 Aug 2005 | PLOS Medicine 10.1371/journal.pmed.0020315

2.2 Vector

Sustained Activation of Akt Elicits Mitochondrial Dysfunction to Block Plasmodium falciparum Infection in the Mosquito Host Shirley Luckhart, Cecilia Giulivi, Anna L. Drexler, Yevgeniya Antonova-Koch, Danielle Sakaguchi, Eleonora Napoli, Sarah Wong, Mark S. Price, Richard Eigenheer, Brett S. Phinney, Nazzy Pakpour, Jose E. Pietri, Kong Cheung, Martha Georgis, Michael Riehle Research Article | published 28 Feb 2013 | PLOS Pathogens 10.1371/journal.ppat.1003180

A Unique Protein Phosphatase with Kelch-Like Domains (PPKL) in Plasmodium Modulates Ookinete Differentiation, Motility and Invasion David S. Guttery, Benoit Poulin, David J. P. Ferguson, Balázs Szöőr, Bill Wickstead, Paula L. Carroll, Chandra Ramakrishnan, Declan Brady, Eva-Maria Patzewitz, Ursula Straschil, Lev Solyakov, Judith L. Green, Robert E. Sinden, Andrew B. Tobin, Anthony A. Holder, Rita Tewari Research Article | published 20 Sep 2012 | PLOS Pathogens 10.1371/journal.ppat.1002948

The JAK-STAT Pathway Controls Plasmodium vivax Load in Early Stages of Anopheles aquasalis Infection Ana C. Bahia, Marina S. Kubota, Antonio J. Tempone, Helena R. C. Araújo, Bruno A. M. Guedes, Alessandra S. Orfanó, Wanderli P. Tadei, Claudia M. Ríos-Velásquez, Yeon S. Han, Nágila F. C. Secundino, Carolina Barillas-Mury, Paulo F. P. Pimenta, Yara M. Traub-Csekö Research Article | published 01 Nov 2011 | PLOS Neglected Tropical Diseases 10.1371/journal.pntd.0001317

Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes. Corby-Harris V, Drexler A, Watkins de Jong L, Antonova Y, Pakpour N, Ziegler R, Ramberg F, Lewis EE, Brown JM, Luckhart S, Riehle MA. PLoS Pathog. 2010 Jul 15;6(7):e1001003. doi: 10.1371/journal.ppat.1001003.

MAPK ERK Signaling Regulates the TGF-β1-Dependent Mosquito Response to Plasmodium falciparum Win Surachetpong, Naresh Singh, Kong Wai Cheung, Shirley Luckhart Research Article | published 03 Apr 2009 | PLOS Pathogens 10.1371/journal.ppat.1000366

Source: PLOS Speaking of Medicine, article by Kasturi Haldar and Margaret Phillips

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