Microbes utilized in healthcare, agriculture, and other fields often face challenging conditions, demanding resilience against extreme temperatures, radiation, and harsh processing methods. A team of ingenious MIT researchers has risen to this challenge, developing a novel technique to empower microbes with the hardiness needed to thrive in these demanding environments.
Their innovative approach involves combining bacteria with a carefully selected blend of food and drug additives classified as “generally regarded as safe” by the FDA. Through rigorous experimentation, the researchers identified specific formulations that effectively stabilize various microbe types, including yeast and bacteria. These formulations demonstrated remarkable resilience against high temperatures, radiation, and the rigors of industrial processing, all of which can be detrimental to unprotected microbes.
Taking their experiment to the ultimate proving ground, the researchers sent some of these fortified microbes to the International Space Station, in collaboration with Space Center Houston Manager of Science and Research, Phyllis Friello. The team eagerly awaits the analysis of these space-faring microbes to assess their ability to withstand the ultimate test of extreme conditions.
“This project focused on stabilizing organisms for extreme conditions, with a broad spectrum of applications in mind, from space missions and human health to agricultural advancements,” explains Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.
Miguel Jimenez, the lead author of the study published in Nature Materials, and a former MIT research scientist now serving as an assistant professor of biomedical engineering at Boston University, highlights the significance of their findings.
The journey began six years ago with funding from NASA’s Translational Research Institute for Space Health (TRISH). Traverso’s lab embarked on a mission to enhance the resilience of beneficial bacteria like probiotics and microbial therapeutics. Their initial analysis of 13 commercially available probiotics revealed a concerning discrepancy: six products contained fewer live bacteria than advertised.
“We observed a significant difference, which wasn’t entirely unexpected,” Traverso reveals. “This prompted us to explore solutions for improvement.”
The team meticulously selected four distinct microbes for their experiments: Escherichia coli Nissle 1917 (a probiotic), *Ensifer meliloti* (a bacterium that enhances plant growth by fixing nitrogen in the soil), Lactobacillus plantarum (a bacterium used in food fermentation), and the yeast Saccharomyces boulardii (also used as a probiotic). Traditionally, microbes are dried into a powder through lyophilization for medical or agricultural use. However, transforming them into more practical forms like tablets or pills poses a challenge, as the process involves exposure to potentially toxic organic solvents. The MIT team sought to identify additives that could enhance the microbes’ ability to survive this process.
“Our goal was to develop a workflow that allowed us to screen materials from the FDA’s ‘generally regarded as safe’ list, combining them with bacteria to identify ingredients that enhance stability during lyophilization,” Traverso explains.
Their innovative setup enabled them to mix microbes with approximately 100 different ingredients, observing their survival rates after 30 days of storage at room temperature. This meticulous process revealed specific ingredients, primarily sugars and peptides, that yielded the best results for each microbe species.
For further optimization, the researchers focused on E. coli Nissle 1917, a probiotic known for treating traveler’s diarrhea. They discovered that a potent combination of caffeine or yeast extract with a sugar called melibiose resulted in an exceptionally stable formulation of E. coli Nissle 1917. This breakthrough formulation, dubbed “formulation D,” enabled survival rates exceeding 10% after six months of storage at 37 degrees Celsius, while a commercially available formulation lost all viability after a mere 11 days under the same conditions.
Formulation D exhibited remarkable resilience against ionizing radiation, withstanding levels up to 1,000 grays. To put this into perspective, the typical daily radiation dose on Earth is about 15 micrograys, while in space, it’s approximately 200 micrograys.
While the precise mechanisms behind the protective effects of these formulations remain a subject of ongoing research, the team hypothesizes that the additives may play a crucial role in stabilizing bacterial cell membranes during rehydration.
To further validate their findings, the researchers conducted stress tests, demonstrating that these resilient microbes not only survive harsh conditions but also retain their functionality. After exposure to temperatures up to 50 degrees Celsius, Ensifer meliloti exhibited an undeterred ability to form symbiotic nodules on plant roots and convert nitrogen to ammonia.
Similarly, their robust formulation of E. coli Nissle 1917 effectively inhibited the growth of Shigella flexneri, a leading cause of diarrhea-related deaths in low- and middle-income countries, when co-cultured in a laboratory setting.
Last year, several strains of these extremophile microbes embarked on a journey to the International Space Station, an endeavor that Jimenez aptly describes as “the ultimate stress test.”
“Even the earthly journey to preflight validation and storage before launch, without temperature control, became part of this test,” Jimenez points out.
With the recent return of these space-faring microbes, Jimenez’s lab is eager to unlock the secrets held within these resilient organisms. Their analysis will compare samples stored inside the ISS with those exposed to the harsh external environment, along with control samples that remained on Earth. Camilla Urbaniak, a research scientist at NASA‘s Jet Propulsion Laboratory, not involved in the study, recognizes the significance of this work. “This research offers a promising approach to enhance the stability of probiotics and/or genetically engineered microbes in extreme environments, such as outer space,” she notes. “This could be instrumental in future space missions, contributing to astronaut health and promoting sustainability through robust and resilient plants for food production.”
This groundbreaking research was made possible by generous funding from NASA’s Translational Research Institute for Space Health, Space Center Houston, MIT’s Department of Mechanical Engineering, 711 Human Performance Wing, and the Defense Advanced Research Projects Agency.
The research paper boasts an impressive roster of contributors, including Johanna L’Heureux, Emily Kolaya, Gary Liu, Kyle Martin, Husna Ellis, Alfred Dao, Margaret Yang, Zachary Villaverde, Afeefah Khazi-Syed, Qinhao Cao, Niora Fabian, Joshua Jenkins, Nina Fitzgerald, Christina Karavasili, Benjamin Muller, and James Byrne, all playing vital roles in this scientific endeavor.
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