Humans may soon owe to a species of small frogs that may give them the power to resist illness. A team of researchers have recently identified a mechanism that gives those ‘super’ frogs the strength to resist pathogens, which opens a new door to repurpose currently used drugs to replicate this power in humans.
During the study, published in the journal Science Advances on June 19, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered genetic and biological mechanisms that enhance the ability of cells and tissues in Xenopus laevis frogs to resist damage in the presence of invading pathogens, suggesting that infections in humans and other animals could one day be treated by increasing their tolerance to pathogens.
The standard approach to treating infections for the last 75 years has been to focus on killing the pathogen, but the overuse of antibiotics in livestock and in humans has led to the emergence of antibiotic-resistant bacteria. However, the super illness-resisting powers Xenopus laevis frogs have inspired the researchers to focus on modifying a host's response to a pathogen rather than killing the pathogen itself.
Research into the biology of disease tolerance has found that it is associated with the activation of stress responses that are normally induced by a low level of oxygen (hypoxia). These cellular responses reprogram T cells, which reduces the amount of inflammation they cause.
As part of the Wyss Institute's ongoing quest to identify drugs that could replicate these biological processes and induce tolerance in humans, the team used a combination of computational techniques and hands-on experiments to tease out the genes and molecular pathways that control tolerance in Xenopus frogs, and then find existing drugs that could activate those pathways and induce a state of tolerance against pathogens in humans.
After examining 30 pharmaceutical drugs, they found three drugs were actually effective for this purpose: FDA-approved deferoxamine, Mimosine, and hydralazine.
