Mutant parasites, unable to infect hosts, highlight virulence genes

May 30, 2007

With a single approach, microbiologists at the University of Wisconsin-Madison have identified dozens of clues to how human parasites may infect their hosts.

The researchers identified nearly 40 genes that, when mutated in the common parasite Toxoplasma gondii, prevented the parasite from forming an infection in the brains of mice. These potential "virulence factors" offer a smorgasbord of promising targets for developing drugs that could block or treat human parasitic infections such as malaria.

The new results are reported online this week in the Proceedings of the National Academy of Sciences.

Though a larger problem in the developing world, parasitic infections are not uncommon in the U.S.

For example, Toxoplasma can infect any warm-blooded animal and is most commonly acquired from improperly cooked meat or by handling feces from infected cats. Pregnant women and people with weakened immune systems are at greatest risk from Toxoplasma infection, which can cause brain damage and death in unborn children and immune-compromised patients, such as AIDS patients.

Despite this, little is known about the factors that regulate parasites' abilities to infect their hosts, says Laura Knoll, professor of medical microbiology and immunology in the UW-Madison School of Medicine and Public Health and UW-Madison Waisman Center.

To study the question, Knoll and her colleagues at UW-Madison and the New York Medical College cast a wide net. Rather than analyze a single gene at a time for a role in virulence, they took the reverse approach, randomly mutating individual genes in the parasites, then looking to see which of the mutant parasites could no longer infect host brains.

"Let's let the parasite tell us what's important," Knoll says.

The broad approach helped them uncover dozens of genes - many of them previously unknown - that may provide new clues about how parasites like Toxoplasma and those that cause malaria, African sleeping sickness and water-borne diarrheal illnesses infect their hosts.

"This screen highlighted genes not previously seen as virulence factors," says Knoll.

From one mutant, Knoll's team pinpointed a gene that acts as a nuclear traffic cop, directing molecular traffic in and out of the parasite's nucleus, where the DNA resides. Mutations in the gene, called RCC1 (Regulator of Chromosome Condensation 1), disrupt the flow of molecules, causing a trafficking breakdown that likely underlies the mutant parasite's inability to effectively sicken its host.

This study is the first evidence that this type of cellular function, called nuclear trafficking, may be important for infectivity, Knoll says.

"We hope to apply what we've learned here to other parasites," she says. "Our goal is to come up with new anti-parasitic drug targets."

Currently, she says, there are few good treatments for most human parasitic infections, and even some of those are very toxic to patients.

RCC1 presents a promising potential target because the parasite versions of the gene are very different from human and other animal versions, which reduces the likelihood of toxic side effects.

Knoll expects research on the other 38 identified virulence factors - still waiting in the wings for additional research - will reveal more insights about parasitic infection. "We know these genes and their functions are important for infection," she says. "We have good targets to go with."

Source: University of Wisconsin

Explore further: Infant failure to thrive linked to lysosome dysfunction

add to favorites email to friend print save as pdf

Related Stories

Obama recommends extended wilderness zone in Alaska

5 hours ago

US President Barack Obama said Sunday he would recommend a large swath of Alaska be designated as wilderness, the highest level of federal protection, in a move likely to anger oil proponents.

NASA craft set to beam home close-ups of Pluto

5 hours ago

Nine years after leaving Earth, the New Horizons spacecraft is at last drawing close to Pluto and on Sunday was expected to start shooting photographs of the dwarf planet.

Navy wants to increase use of sonar-emitting buoys

6 hours ago

The U.S. Navy is seeking permits to expand sonar and other training exercises off the Pacific Coast, a proposal raising concerns from animal advocates who say that more sonar-emitting buoys would harm whales and other creatures ...

Uganda seizes massive ivory and pangolin haul

7 hours ago

Ugandan wildlife officers have seized a huge haul of elephant ivory and pangolin scales, representing the deaths of hundreds of endangered animals, police said Sunday.

Recommended for you

Infant failure to thrive linked to lysosome dysfunction

Jan 27, 2015

Neonatal intestinal disorders that prevent infants from getting the nutrients they need may be caused by defects in the lysosomal system that occur before weaning, according to a new Northwestern Medicine ...

Gene may open door for improved keloid, scar treatment

Jan 23, 2015

Researchers at Henry Ford Hospital in Detroit have identified a gene that may offer a better understanding of how keloid scars develop and potentially open the door to improved treatment for the often painful, ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.