Apicomplexa is the name of a large group of microorganisms that include the causes of malaria and toxoplasmosis. Presently, their complexities make studying these parasites difficult, but a new model system may faciliate new research. This was reported on February 15, 2008 in the open-access journal PLoS Pathogens, a part of the Public Library of Science.

Researchers from the University of Georgia and Montana State University have generated a method of conducting powerful genetic studies of Apicomplexa parasites, beginning with Toxoplasma (the source of toxoplasmosis,) as a model. In the method developed by the team, large numbers of mutant parasites with defective growth were created, along with tools to identify the genes containing the mutations. Together, these will allow scientists to discover new genes behind the biological processes essential to the parasites’ success.

Previously, traditional model organisms such as yeast or E. coli have been used by researchers to study the biological processes of Apicomplexa. The results using these models has been mixed because biological matches are difficult to find between these organisms. Thus, many parts of the Apicomplexa life and pathogenesis are still poorly understood at a mechanistic level.

Toxoplasma gondii, the cause of toxoplasmosis, was the organism examined in this particular study. While its primary host is the cat, it can be carried in most warm-blooded animals. Infection is usually benign — in fact, twenty percent of the U.S. population is chronically infected with the pathogen. However, severe disease can occur in immune suppressed individuals, such as pregnant women or people with HIV/AIDS. T. gondii proved a strong new model organism because its microscopic structures are clearly defined, its culture and manipulation is relatively simple, and it is already generally better understood than many Apicomplexa.

The tools developed specifically targeted the unusually “flexible” life cycle of the cells, but it should have implications for other facets of parasite biology. “Using this new approach, we have genetically dissected the way the parasite divides and multiplies within its host cell,” stated co-author Boris Striepen. “Importantly, this approach should be broadly applicable, allowing unbiased genetic analysis of any part of parasite biology for which a screen can be devised using this model.” An understanding of how these parasites function is especially valuable because they infect a variety of vertebrate and invertebrate animals, and they occupy an intracellular niche that allows them shelter from the immune system and regular nutrients.

The paper published in PLoS Pathogens describes an analysis of the apicomplexan cell division machinery in T. gondii, but the implications of these techniques have the potential to be far reaching in terms of global public health. In particular, this new system could provide valuable information about other Apicomplexa such as Plasmodium, the organism which causes malaria. Malaria presently infects hundreds of millions of people a year, killing between one and three million, most of whom are children in Sub-Saharan Africa.

“Protozoans causing malaria and other serious diseases affect millions of people across the planet,” says co-author Michael White. “These are clever parasites that grow inside our own cells, and the more they grow, the greater damage they cause. What we have done in the work published in the PLoS paper is open the door to the critical genes that these parasites must express in order to grow. These are the `Achilles heels’ of this pathogen family. Many of the genes are unique and could give us valuable leads on how we might stop parasite growth and prevent disease.”

Finally, drug development to combat these diseases encounters many problems, because Apicomplexa are eukaryotic organisms. Since they have nucleii, many of the metabolic pathways employed are very similar to those of their animal hosts. This means that many drugs meant to kill or damage the parasites will also have deleterious effects on the host animals. With a richer understanding of how Apicomplexa work on a cellular and molecular level, it will be possible to uncover differences in biology that can be exploited for the design of drugs and vaccines.

Forward Genetic Analysis of the Apicomplexan Cell Division Cycle in Toxoplasma gondii
Marc-Jan Gubbels, Margaret Lehmann, Mani Muthalagi, Maria E. Jerome, Carrie F. Brooks, Tomasz Szatanek, Jayme Flynn, Ben Parrot, Josh Radke, Boris Striepen, Michael W. White
PLoS Pathog 4(2): e36. doi:10.1371/journal.ppat.0040036
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Written by Anna Sophia McKenney