For millennia, the baker’s yeast—a humble fungus—has helped humans to bake bread and brew alcoholic drinks. In recent decades, it has also become a darling of laboratory science—it is easy to grow, study, and genetically manipulate, and it provides scientists with important clues about how our own cells work. Now, thanks to Nili Ostrov and colleagues at Columbia University, baker’s yeast is about to begin yet another career—as a biosensor for detecting cholera and other diseases.
Cholera is caused by a bacterium called Vibrio cholerae, which lives in salty water and lashes itself to the shells of small crustaceans. If it finds its way into our drinking supplies, and into human bodies, it can cause severe diarrhea, which can be fatal if left untreated. If such infections aren’t controlled quickly, they can flare into massive epidemics. One, currently going on in Yemen, has already infected 200,000 people and is afflicting 5,000 more every day. Another, which began in Haiti in 2010 and continues to this day, has already affected 7 percent of the country’s population.
Currently, scientists detect V. cholerae by growing the bacterium in Petri dishes—a laborious process that takes a day or two. That’s too slow. To control cholera outbreaks, researchers need faster ways of detecting the bacterial culprits. Ideally, you’d have something that works like a home pregnancy kit—a simple dipstick that would give a clear answer after being dunked in water. The Columbia team has now created a prototype for such a device, using yeast.
Ostrov and her colleagues, Miguel Jimenez and Sonja Billerbeck, genetically engineered yeast cells so they produce a red chemical when they come into contact with the right target. The cells can be dried and added to paper, which then reddens when it touches contaminated water. “Our vision is that we can just give the yeast to a resource-poor country, and they can grow the biosensor themselves just like they can brew beer,” says Virginia Cornish, who led the team.
Before going after cholera, the team cut their teeth on a simpler goal—they tweaked yeast to detect other kinds of fungi that cause disease. Fungal cells are studded with molecules called mating receptors, which recognize the pheromones released by their own kind. Each species has its own distinctive receptors, and by swapping these around, the team could tune baker’s yeast to the scents of other fungi. They began with Candida albicans, the species that causes thrush. Eventually, they built sensors for nine other infectious fungi, including some that cause human diseases, and others that cause devastating blights in rice and wheat.
In each case, the team connected the mating receptors to genes that make lycopene—the chemical that makes tomatoes red. When the yeasts encounter the right target, they become redder. “Within 3 hours, you get a yes-or-no answer that’s visible to the naked eye,” says Cornish. “And now that we have the tech figured out, it should be really straightforward to develop new biosensors for new targets.” These include the bacteria behind cholera.
The team loaded their engineered yeasts onto simple dipsticks that could be used to analyze soil, urine, blood, and water. They give clear readouts, and can be stored for at least nine months at room temperature. They’re a little slow, but they're still much faster than growing microbes in a lab to confirm their presence. Cornish also likes the idea of abandoning the dipsticks altogether and making the yeast available as sachets of powder. Empty them into a cup of suspicious water, and they’ll turn red if there’s something nasty within.
These tests ought to be cheap to produce. “Our back-of-the envelope calculations say that the biosensor can be made for less than one cent a test.” By contrast, dipsticks that detect cholera using antibodies cost a hundred times as much, because those antibodies need to be mass-produced and purified. The yeast, by contrast, can be handed out and grown as they have been for centuries. As Ostrov says, “Baker’s yeast bridges the gap between lab research and household products.”
“This is creative work,” says Baojun Wang, a synthetic biologist from the University of Edinburgh. “There’s huge potential for engineering cell-based biosensors for detecting a whole array of targets, including bacteria, viruses, and toxins, in resource-limited situations.”
The team is now tweaking their yeast sensors to make them faster, more sensitive, less likely to mistakenly react to the wrong targets, and as user-friendly as possible. “Scientists are used to developing very sophisticated, research-oriented tools, but we wanted to develop a product that people can actually use,” she says. To that end, her team are talking with public health experts, and people who have dealt with cholera outbreaks in the field, to ensure that their test will be as practical as possible.
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