Researchers Decipher Cause Of Parasite's Worldwide Spread

Parasite life cycles are complex and thought to develop over long periods with their hosts. This study reveals that parasites sometimes adapt rapidly to new hosts, indicating that host-parasite relationships may not always represent stable, long-term associations.

"Our findings raise the possibility that other parasites may also radically change their lifestyle by a similar mechanism and hence present new threats of infection" says study leader L. David Sibley, Ph.D., associate professor of molecular microbiology. The work is published in the Jan. 17 issue of the journal Science.

About 35 million people in the United States - and up to a quarter of the world's population - are thought to be chronically infected with Toxoplasma. However, only people with weakened immunity typically develop severe toxoplasmosis, a potentially serious disease that can lead to birth defects, brain inflammation and vision problems. The infection usually is acquired by accidentally swallowing spores from contaminated soil, water, cat litter or objects that have had contact with cat feces. The infection also can be acquired from eating raw or partially cooked meat, especially chicken, pork, lamb or venison.

While eating infected meat easily spreads Toxoplasma from animal to animal, related parasites have highly restricted life cycles and require that a specific carnivore eat a specific herbivore for transmission to occur.

Toxoplasma also is unusual in that worldwide there are only three main strains, whereas related parasites typically have many distinct strains. Research has shown that the three strains are highly similar genetically and arose from a single mating event between two parent parasites. In the present study, members of Sibley's laboratory, working closely with colleagues at Cambridge University and the University of Georgia, determined how long ago that mating event occurred. They first estimated the rate at which mutations arise in Toxoplasma. They then sequenced a select set of genes from the three strains to determine how many mutations were present. That data, along with estimates of the mutation rate, indicate that the three strains arose from a common ancestor no more than 10,000 years ago.

"That's the blink of an eye in evolutionary time," says Sibley.

During that blink, however, the new strains managed to infect a wide range of animal species and spread worldwide, suggesting that they had undergone some fundamental change. To explain how that happened, Sibley and his colleagues hypothesized that the parasite's life cycle had been altered, facilitating much more efficient spread.

The investigators compared the young strains to less common, older strains of Toxoplasma. They found that the young strains have a heightened ability to infect animals that have eaten the cysts that form in the meat of infected animals. Normally such tissue cysts are infectious only to a single species of animal, typically a carnivore that serves as the definitive host where sexual replication occurs. The ability of the young Toxoplasma strains to bypass this restriction allows them to infect many different hosts, where they again form cysts and reproduce asexually.

"Direct oral infectivity after eating tissue cysts is seen only in Toxoplasma and this trait is exemplified by these young strains," says Sibley. "This strongly suggests that the unique combination of genes passed along during that one mating event endowed the three young strains with an ability to more effectively spread throughout the food chain."

The findings demonstrate that changes in the infectiousness of parasites can occur not just through new mutations but also through a reshuffling of existing genes.

"This was a big surprise," says Sibley. "We have always appreciated that genetic recombination could cause subtle changes in an organism, but this is an extreme change: It produced a completely new lifestyle and removed a major barrier to infection."

Sibley and his colleagues now are studying genetic differences between the young and old strains of the parasite to learn more about how the newly derived strains can infect so many hosts.

"If one wanted to make a vaccine against this parasite, those genes and their products might be good ones to target," says Sibley.

###

Su C, Evans D, Cole RH, Kissinger JC, Ajioka JW, Sibley LD. Recent expansion of Toxoplasma through enhanced oral transmission. Science, Jan. 17, 2003.

Funding from the National Institute of Allergy and Infectious Diseases, the Biotechnology and Biological Sciences Research Council And the Burroughs Wellcome Fund supported this research.