Evolution of Pathogens Holds Promise for Revolutionary Anti-Parasitc Treatments
An ancestor of algae may be a new target for preventing parasitic cells from replicating.
--by Alexia Severson
Based on evolutionary history, researchers at the University of Georgia have discovered a new way to prevent harmful parasitic cells from replicating inside their host and causing disease, according to research published in the open access journal PLOS Biology.
Apicomplexa, parasites that causes some of the world’s most prevalent diseases, including malaria and toxoplasmosis, evolved from algal ancestors millions of years ago and were once a group of small, single-celled algae that swam through the ocean by beating whip-like tails, called flagella. However, according to researchers, throughout evolution these parasites have re-purposed; they no longer use flagella to swim, but to organize the assembly of an invasive cell.
Apicomplexa must invade an animal or human and force its way into the cells of its host in order to survive. Once inside, it begins to replicate, spreading the infection throughout the host's body. During the process of replication, the parasite cell loads genetic material into its daughter cells through a strand of fiber connecting the two. Researchers have found that by altering the genes for components of this fiber, they can stop this replication, rendering the parasite harmless. Researchers also suggest that with further study, this algae-based connective fiber may serve as a promising target for the development of future anti-parasitic drugs.
The Expert Take
The study authors say it is important for scientists to pay close attention to the evolutionary history of the organisms they study because it not only allows them to gain a better understanding of the pathogens they are trying to fight, but also provides opportunities to develop novel treatments.
“Evolution matters,” said Boris Striepen, a professor at the University of Georgia’s Department of Cellular Biology and senior author of the study. “Understanding the evolution of a pathogen—in this case, its origin as a flagellated alga—allows us to understand its present. In this study we were able to demonstrate that the mechanisms that previously organized the flagellum now organize the invasion machinery used by the parasite to force its way into our cells during infection.”
Striepen said this research provides scientists with a new way to understand parasite division and replication. However, additional research is needed in order to fully understand how a cell evolves and adapts to a life as a parasite.
“Understanding the fundamental biology of pathogens will also allow us to identify and pursue new targets for drug development,” he said. “The particular proteins described in this study are not present in the human host.”
Source and Method
To understand the evolution and structure of these parasites, researchers constructed tagged reporter parasites, using T. gondii RH strain parasites, as well as Conditional SFA2 and SFA3 knock out parasites.
Tests included protein expression and antibody production, fluorescence microscopy, electron microscopy, and western blotting.
According to The National Center for Biotechnology Information, “more than three billion people live in malarious areas, and the disease causes between one million and three million deaths each year.” But according to researchers, treatments for diseases like malaria are jeopardized by the parasite becoming resistant to available drugs.
Fortunately, this research provides a new understanding of the parasites that cause these deadly diseases, and as Striepen pointed out, may provide future therapies and new anti-parasitic drugs that can neutralize these parasites before they become harmful.
Several studies have taken various approaches to analyzing the evolution of parasites. A study published in 1998 in PNAS, looked at the evolution of primate malaria parasites based on the gene encoding cytochrome b from the linear mitochondrial genome. Researchers studied 17 species of Plasmodium, including 14 that are parasitic in primates, and found that the primate malaria parasites originated in Africa.
An article published in 2008 in Molecular Phylogenetics and Evolution discussed phylogenetic analysis of genomic data and its insights into the evolutionary history of pathogens. Here, the author states that “hundreds, perhaps thousands, of malaria parasite species exploit squamate reptiles, birds, and mammals as vertebrate hosts” and that “the evolutionary and ecological events that led to this diversification and success remain unresolved.”
Another study, published in the Japanese Journal of Infectious Diseases in 2012, looked at drug resistance and the evolution of plasmodium falciparum, responsible for the most severe form of malaria in humans, stating that “an inadequate understanding of a mechanism of artemisinin resistance and the lack of reliable genetic markers to monitor artemisinin resistance make it difficult to survey the spread of resistance.”