Science adv, 2017
Researchers have developed a tool that is likely to revolutionize the way we detect and treat pathogens in everything from human health to agriculture to water. Using only common household baker's yeast, they've created an extremely low-cost, low-maintenance, on-site dipstick test they hope will aid in the surveillance and early detection of fungal pathogens responsible for major human disease, agricultural damage and food spoilage worldwide. The study appears in the journal Science Advances.
"Our biosensor allows us to detect a pathogen for less than one cent per test; it is easy to use, cheap to produce and doesn't require cold-storage facilities," said Principle Investigator. "It stands to impact agriculture and health, especially in developing countries, where it is arguably needed the most. We're excited about the possibilities."
Around the globe, fungal pathogens present an increasingly urgent public health burden, causing an estimated two million deaths annually and inflicting devastating losses on plant crops and population decline in animal wildlife. Still, fungal pathogens and the diseases they cause are often neglected and research to combat them is underfunded.
To address this problem, and in close collaboration with experts in public health the team swapped out naturally-occurring cell surface receptors of Saccharomyces cerevisiae, or baker's yeast, with pathogen-specific receptor proteins. They started by building a biosensor for the detection of Candida albicans, a human fungal pathogen (a type of yeast) that occurs naturally in the human gut, but can cause serious medical problems and even death if the population gets out of control.
After replacing bakers yeast's natural receptor with that of C. albicans, the researchers then altered its DNA to enable production of lycopene, the pigment responsible for the red coloring of tomatoes. This allowed the engineered yeast to turn red when in the presence of a target molecule, in this case, C. albicans fungus pheromones.
The experiment was a breakthrough success. The sensor turned red when exposed to the fungal target. The team had developed a functional, simple, highly-specific, one-component sensor using only yeast.
Next, the researchers successfully tested their assay for the ability to detect ten additional major pathogens, including Paracoccidioides brasiliensis, a fungus responsible for a progressive tropical disease affecting the mucosa in the nose, sinuses and skin, and Botrytis cinerea, a grey mold that causes substantial crop loss worldwide. In each case, the test functioned accurately without sacrificing any of the sensitivity and specificity attainable with other, significantly more expensive tests.
With an operational assay in-hand, the team set out to make it versatile and user-friendly, designing a one-step rapid dipstick prototype, much like an at-home pregnancy test, that can be used in complex samples, including whole blood, serum, water, urine and soil.
"New research in the area of synthetic biology has given us the ability to leverage live cells in the development of much more specific and helpful tools than we have had in the past," senior author said. "Our assay can be cheaply made, economically produced at large-scale, widely distributed as a stable dried product for household use, robustly applied to complex samples, is not reliant on cold-chain storage, and can be readily detected by the eye without additional equipment, making it a compelling and completely feasible tool for surveillance of pathogens around the globe. This is critical for human health, food security, bioterrorism, and maintenance of biodiversity."
The Columbia team is currently in conversations with global health non-profits and worldwide research, technology, development and citizen groups to determine the needs of specific countries. They believe there are many more applications for their sensor, including use in virus and bacteria detection, and a biosensor for cholera, a potentially-lethal diarrheal disease caused by the ingestion of food or water contaminated with the bacterium Vibrio cholera, is in the works to aid in African surveillance efforts.
http://advances.sciencemag.org/content/3/6/e1603221
Yeast-based biosensor for pathogen detection
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