Researchers studying the cat-poop parasite, Toxoplasma gondii , made abreakthrough that will spare a lot of felines from research.
Of the many parasites known to control the mind of their host, none is morefamous than Toxoplasma gondii —the single-celled organism known colloquiallyas Toxo. It can survive in a variety of animals, but it only reproducessexually in cats. If it gets into mice or rats, it alters their behavior sothey become fatally attracted to the scent of feline urine. They get eaten,the cat gets infected, and Toxo gets to make more Toxo.
Toxo infects more than a third of the world’s people, spreading throughundercooked meat or food or water contaminated by infected cat waste (butnot through direct contact with cats). In most cases, the parasite isharmless, and much-hyped claims that it affects human behavior are weak. Butit can also pass from mother to fetus, causing blindness, developmentalproblems, hydrocephalus, and other disabilities. There is no vaccine or cure,and research has been generally slow and difficult, which Toxo’s cat-dependentlife cycle doesn’t help.
To study Toxo, researchers need large stocks of the parasite, which meansraising, infecting, and sacrificing cats. For almost four decades, thatunenviable task fell to a small USDA lab in Maryland, but the agency recentlydecided to shut down the facility after pressure from animal-rights activists.That’s good news for the cats, but bad news for the already sluggish quest tolearn more about Toxo.
Now Laura Knoll of the University of Wisconsin at Madison has thrown herfellow researchers a lifeline. Her team finally worked out why Toxo only hassex in cats. It then used that knowledge to break the species barrier,allowing the parasite to complete its life cycle in mice for the first time.The study is available online and is set to be published in a scientificjournal after three reviewers described it as “truly remarkable,”“transformative,” and “a key breakthrough.”
Read: How cats used humans to conquer the world
“It’s a major finding,” Rima McLeod of the University of Chicago MedicalCenter told me. “It’s the first time that the cat cycle has been recapitulatedoutside of cats.” That breakthrough could spare a lot of felines, andcompensate for the closure of the Maryland facility. “Now we won’t have to usecompanion animals, which will make a lot of people happy, including us,” Knollsays. “No one wants to use cats in their research.”
At first, Knoll’s colleagues Bruno Di Genova and Sarah Wilson tried rearingToxo on cat organoids—lab-grown balls of feline intestinal tissue. It didn’twork: The parasites grew, but never reached the sexual stage. The teamwondered whether it had missed an important nutrient; perhaps a fatty acid,which Toxo is known to scavenge from its hosts. And sure enough, when the teamadded linoleic acid, “we had sex all over the place,” Knoll says.
Our guts convert linoleic acid into other substances that regulate our immunesystems, control blood pressure, and more. This transformation depends on anenzyme called delta-6-desaturase, or D6D for short. And cats, it turns out,are the only mammals that don’t make D6D in their guts. They can still producethe enzyme in other organs, but they shut it off in their intestines. Knollsuspects that they did so because they evolved in desert environments, andadapted by preserving their fatty acids. Indeed, linoleic acid makes up 25 to46 percent of fatty acids in a cat’s blood, but just 3 to 10 percent of thosein a mouse’s.
Cat-food manufacturers and other researchers figured these details out in the1970s, Knoll says, but the Toxo community was largely unaware of them. Andyet, they perfectly explain the parasite’s life cycle. Toxo only has sex incats because it depends on linoleic acid, and cats are the only mammals thatbuild up enough of the stuff. “Whenever I give talks, I often get thequestion: Why the cats? What’s special about the cats?” Knoll says. “Now wehave an answer.”
Once the team figured out that linoleic acid was the key, it set about tryingto figure out how to shut down D6D in mice. Fortunately, a drug that blocksthe enzyme was commercially available. The team fed it to mice, along with alinoleic-rich diet and some Toxo. After a week, it saw signs that theparasites had reached the sexual stage, and were making oocysts, the sporelikestructures that spread Toxo infections to new hosts. “The first experiment wedid, we could see oocysts being pooped out in the mouse feces,” Knoll says.“That was super cool.”
The case is not quite a slam dunk, notes Isabelle Coppens of the Johns HopkinsBloomberg School of Public Health. Toxo researchers still don’t have enoughtechniques for conclusively identifying sexual-stage parasites, she says, andthe oocyst images in Knoll’s paper are a little blurry. Still, “I believe thatthere is something hot in this piece of work,” she says, “and the implicationswill be huge.”
Read: Cats are not medicine
Science journalists are often mocked for describing preliminary discoveries inmice that may or may not translate to humans. There’s even a Twitteraccount—@justsaysinmice—that retweets overhyped news stories with “IN MICE”appended overhead. It’s delightful, then, to write about a study in whichdoing something in mice is the entire point.
Knoll is now trying to delete the gene for D6D in mice, to create a strain oflab rodents that can host Toxo without the need for any drug. Her successwould greatly accelerate the pace of Toxo research, because scientists couldstudy the parasite using a common lab animal that’s more familiar and easierto work with. “It is extremely important for the field,” says John Boothroydof the Stanford University School of Medicine. “We probably know over 100times more about the mouse and have far more than 100 times more reagents forits study than we do for felines.”
Many important techniques in modern biology rely on cross-breeding differentstrains of a given organism—and that’s hard when said organism only has sex incats. For the past three decades, in order to cross-breed Toxo, “you’d have toinfect mice with your strains, wait 30 days, and send their brains to the USDAin Maryland, where they would feed [the organs] to cats and send you back catshit,” Knoll says. If that process becomes simpler, it may be quicker to findtreatments and vaccines—for cats, as well as humans.
Source: Ed Yong – The Atlantic
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