Fighting malaria through mathematical analysis of parasite's metabolismMarch 23, 2017
A new mathematical model, based on the deadliest malaria parasite, Plasmodium falciparum, could help develop antimalarials by identifying key metabolic targets, according to a study published in PLOS Computational Biology by Vassily Hatzimanikatis at École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, and colleagues.
Malaria, a mosquito-borne infectious disease caused by parasites of the Plasmodium genus, is becoming increasingly difficult to treat as the parasites develop resistance to current drugs. A promising new strategy is to target the parasites' metabolism, but it has proven to be both versatile and complex, making it difficult to target. It has also been difficult to integrate existing experimental data on the metabolism with genetic data on the genome sequence, gene expression, and essential genes for growth.
To overcome these obstacles, the authors of the present study developed a model that accurately connects experimental information from both genetics and metabolomics. They looked at the thermodynamic properties of the metabolic reactions, which relate to the way the parasites use and produce energy. This focus on the energetics of the reactions allows them to analyse, for the first time, which metabolic functions are thermodynamically coupled and are essential during infection. It reveals complex interactions between the parasites' genes and metabolism, which, the authors state, could identify potential mechanisms to target with drugs.
"The model integrates all available knowledge on the genetics and metabolism of the parasites and allows the formulation of testable hypotheses behind the parasite's essential functions," says Dr. Hatzimanikatis. "Ultimately, it can accelerate the discovery toward novel antimalarial drug targets."
The EPFL scientists will now continue to calibrate and improve the predictive capabilities of the model with additional genetics and metabolomics data provided by collaborators from the MalarX.ch consortium in the University of Geneva and Bern and the Wellcome Trust Sanger Institute. They hope to reveal the mechanisms behind host-pathogen interactions and gain insight into the physiology of the parasite while it is dormant.
This press release is based on text provided by the authors.
Citation: Chiappino-Pepe A, Tymoshenko S, Ataman M, Soldati-Favre D, Hatzimanikatis V (2017) Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks. PLoS Comput Biol 13 (3): e1005397. doi:10.1371/journal.pcbi.1005397
Funding: VH, DSF, ACP, ST, and MA are supported by the RTD grants MalarX and MicroScapesX within SystemsX.ch, the Swiss Initiative for Systems Biology evaluated by the Swiss National Science Foundation: http://www.systemsx.ch/index.php?id=276&L=3 and http://www.systemsx.ch/index.php?id=277&L=3. VH, ACP, ST and MA are supported by the Ecole Polytechnique Federale de Lausanne. DSF is supported by the University of Geneva. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Related Malaria Articles:
Malaria is a global killer and a world health concern.
Scientists have discovered a gene that allows to double the production of artemisinin in the Artemisia annua plant.
EPFL scientists have fully modeled the metabolism of the deadliest malaria parasite.
Should we commit to eradicate malaria worldwide, asks a debate article published by The BMJ today?
An investigational malaria vaccine given intravenously was well-tolerated and protected a significant proportion of healthy adults against infection with Plasmodium falciparum malaria -- the deadliest form of the disease -- for the duration of the malaria season, according to new findings published in the Feb.
Malaria mosquitoes prefer to feed -- and feed more -- on blood from people infected with malaria.
A lineage of multidrug resistant P. falciparum malaria superbugs has widely spread and is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for the main falciparum malaria medicines, artemisinin combination therapies (ACTs), according to a study published today in The Lancet Infectious Diseases.
The goal of eliminating malaria in countries like India could be more achievable if mosquito-control efforts take into account the relationship between mosquitoes and cattle, according to an international team of researchers.
Giving preventive antimalarial drugs to children up to age 10 during active malaria season reduced the cases of malaria in that age group and lowered the malaria incidence in adults, according to a randomized trial carried out in Senegal and published in PLOS Medicine by researchers from the Université Cheikh Anta Diop, Senegal, the London School of Hygiene & Tropical Medicine, UK, and other collaborators.
OIST researchers reconstruct the 3-D structure of a malaria protein in combination with human antibodies.
Related Malaria Reading:
The Fever: How Malaria Has Ruled Humankind for 500,000 Years
by Sonia Shah (Author)
In recent years, malaria has emerged as a cause celebre for voguish philanthropists. Bill Gates, Bono, and Laura Bush are only a few of the personalities who have lent their names--and opened their pocketbooks--in hopes of stopping the disease. Still, in a time when every emergent disease inspires waves of panic, why aren't we doing more to tame one of our oldest foes? And how does a pathogen that we've known how to prevent for more than a century still infect 500 million people every year, killing nearly one million of them?
In The Fever, journalist Sonia Shah sets out to answer those... View Details
The Malaria Project: The U.S. Government's Secret Mission to Find a Miracle Cure
by Karen M. Masterson (Author)
A shocking exposé of America’s secret mission to combat malaria during World War II with a campaign that tested experimental drugs on men gone mad from syphilis.
Foreseeing the need for a malaria drug, American war planners re-created Germany’s research model, then grew it tenfold. Spearheading the effort, Dr. Lowell T. Coggeshall recruited private corporations as well as chemists from Harvard and Johns Hopkins to make novel compounds, which were then tested on human subjects.
By 1943, a dozen strains of malaria were injected into mental health patients and convicted... View Details
The Making of a Tropical Disease: A Short History of Malaria (Johns Hopkins Biographies of Disease)
by Randall M. Packard (Author)
Malaria sickens hundreds of millions of people―and kills one to three million―each year. Despite massive efforts to eradicate the disease, it remains a major public health problem in poorer tropical regions. But malaria has not always been concentrated in tropical areas. How did other regions control malaria and why does the disease still flourish in some parts of the globe?
From Russia to Bengal to Palm Beach, Randall Packard’s far-ranging narrative traces the natural and social forces that help malaria spread and make it deadly. He finds that war, land development, crumbling... View Details
First Comes Love, then Comes Malaria: How a Peace Corps Poster Boy Won My Heart and a Third World Adventure Changed My Life
by Eve Brown-Waite (Author)
In this hilarious memoir, a pampered city girl falls head over little black heels in love with a Peace Corps poster boy and follows him— literally to the ends of the earth.
Eve Brown always thought she would join the Peace Corps someday, although she secretly worried about life without sushi, frothy coffee drinks and air conditioning. But with college diploma in hand, it was time to put up or shut up. So with some ambivalence she arrived at the Peace Corps office, sporting her best safari chic attire, to casually look into the steps one might take to become a global... View Details
Malaria: Biology in the Era of Eradication (Cold Spring Harbor Perspectives in Medicine)
by Dyann Wirth (Editor), Pedro L. Alonso (Editor)
Malaria is a mosquito-borne disease caused by parasitic protozoa that belong to the genus Plasmodium. This disease imposes a significant global health burden, claiming the lives of several thousand children and pregnant women each day. Increasing antimalarial drug resistance and the complexity of the Plasmodium life cycle, among other factors, have made eradication difficult.
Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the biology, pathology, and epidemiology of malaria, as well as... View Details
Malaria Dreams: An African Adventure
by Stuart Stevens (Author)
While attempting to transfer a friend's Land Rover from the Central African republic to Europe, two travel companions experience various adventures and hijinks in such locales as Lake Chad, Timbuktu, and the Sahara View Details
The Long Struggle against Malaria in Tropical Africa
by James L. A. Webb Jr (Author)
The Long Struggle Against Malaria in Tropical Africa investigates the changing entomological, parasitological, and medical understandings of vectors, parasites, and malarial disease that have shaped the programs of malaria control and altered the transmission of malarial infections. It examines the history of malaria control and eradication in the contexts of racial thought, population movements, demographic growth, economic change, urbanization, warfare, and politics. It will be useful for students of medicine and public health, for those who are involved with malaria research studies, and... View Details
Malaria (1989): Host Responses to Infection (CRC Press Revivals)
by CRC Press
The purpose of this book is to analyze and determine how a host responds to a blood stage malaria infection. It focuses on strategies for anti-malarial vaccination, genetic control of host resistance to malaria, and the contribution of the host genetic background to resistance or susceptibility to malaria. This book is an important reference work for anyone who studies the field of microbiology, immunology, or parasitology. View Details
Malaria: Poverty, Race, and Public Health in the United States
by Margaret Humphreys (Author)
In Malaria: Poverty, Race, and Public Health in the United States, Margaret Humphreys presents the first book-length account of the parasitic, insect-borne disease that has infected millions and influenced settlement patterns, economic development, and the quality of life at every level of American society, especially in the south.
Humphreys approaches malaria from three perspectives: the parasite's biological history, the medical response to it, and the patient's experience of the disease. It addresses numerous questions including how the parasite thrives and eventually... View Details
PLAQUENIL Tablet: Prevents and Treats Acute Attacks of Malaria; and also Used to Treat Lupus and Rheumatoid Arthritis
by James Lee Anderson (Author)
“Although, your health condition may impact your everyday life, do not let it define who you are.” PLAQUENIL (hydroxychloroquine) is used to prevent and to treat malaria and to treat some conditions such as liver disease caused by protozoa. It is also used in the treatment of arthritis to help relieve inflammation, swelling, stiffness, and joint pain and to help control the symptoms of lupus erythematosus (lupus; SLE). Hydroxychloroquine belongs to the family of medicines called antiprotozoals. Protozoa are tiny, one-celled animals. Some are parasites that can cause many different kinds... View Details