Fungi are a microscopic menace to global health and food security. More than 1 billion people are infected with disease-causing species worldwide, while other strains flourish in wheat, corn, and other crops, where they destroy food harvests. Now, a cheap and simple method that can easily detect the fungus among us without sophisticated lab equipment could help developing countries save millions of lives by diagnosing infections and finding contaminated crops and food.
“This is highly commendable and a great achievement,” says Maurice Boissinot, a microbiologist who designs biosensors at Laval University in Quebec City, Canada, but was not involved in the new research. “The way they engineered [the test] is truly something.”
Fungi come in many forms, some less benign than others. In addition to species that cause common skin infections such as ringworm and athlete’s foot, other strains cause internal infections that can lead to painful mouth lesions, swollen lymph nodes, and even death. Detecting these infections isn’t too hard for well-equipped labs and hospitals. But most tests rely on antibodies that bind fungal proteins or reading nucleic acids to identify fungi by their genes, thus requiring sterile labs and refrigerated reagents that doctors and farmers in developing countries often don’t have access to.
Just like a village can brew their own beer, they could now brew their own yeast diagnostics.
So Virginia Cornish, a synthetic biologist at Columbia University, and her team set out to develop an alternative test with a long shelf life and no refrigeration using Saccharomyces cerevisiae, commonly known as baker’s yeast, as their model fungus. Like many other fungi, Baker’s yeast has mating receptors, proteins on its cell surface that detect pheromones released by potential partners. Cornish’s team took a mating receptor gene from Candida albicans, a common cause of yeast infections in humans, and stuck it in the baker’s yeast. They also added several other genes that they put under the receptor’s control—snippets that allow the yeast to produce lycopene, the red pigment and antioxidant abundant in tomatoes. In essence, the team turned the baker’s yeast into a biosensor that blushes tomato red upon detection of C. albicans. What’s more, the test yields results in just 3 hours, they report today in Science Advances.
Cornish wanted to expand the variety of fungal infections that their system could detect. The team found that simply replacing the baker’s yeast mating receptor gene with similar genes from other pathogenic species—including Magnaporthe oryzae, which causes blast disease in rice, and Fusarium graminearum, which causes blight disease in wheat and barley—allowed them to create a total of 10 new strains that can each detect a different disease.
To make the yeast biosensor user-friendly, they soaked it into a paper dipstick that can easily test blood, urine, water, and dirt. The dipstick, which contains a live version of the genetically modified baker’s yeast, still worked after being stored at room temperature for 38 weeks. “Just like a village can brew their own beer, they could now brew their own yeast diagnostics,” Cornish says. “And it is very low tech.”
Keith Pardee, a synthetic biologist at the University of Toronto in Canada who developed paper-based screens for Zika virus, says he is excited by the new test. “Since this yeast is already found in the kitchen, it seems like a pretty natural fit for monitoring fungal contamination of food.”
But Boissinot cautions that the sensor is not ready for deployment in the clinic. In a crucial test of their sensor, the researchers used higher levels of fungal pheromones than those normally found in patient blood or urine samples. And yeast biologist Joseph Heitman at Duke University in Durham, North Carolina, says that previous studies have shown some yeast mating receptors might respond to pheromones from similar species. That means that the biosensor could potentially misidentify some of the fungal diseases they are trying to detect.
“We are not a game-changer yet,” Cornish concedes, “but we are working on improving this now.” Her team is also planning to develop a similar biosensor that can detect bacterial pathogens, including microbes responsible for cholera and the devastating citrus greening disease threatening Florida’s orange orchards. “This biosensor is impressive, and we should do more to make the microbes work for us, not against us,” Boissinot says. “It is going to be useful in the future, I am convinced about that.”