To treat or to tolerate (pathogens), that is the question: Research in frog embryos identifies drugs that could be repurposed to treat infections in mammals by inducing tolerance to pathogens

Why do some people seem to never get sick while others consistently fall prey to viruses and bacteria? How can the spouse of a sick person avoid catching their partner’s bug despite sleeping next to them every night? Questions like these have become top-of-mind for many people during the COVID-19 pandemic, and scientists are now a big step closer to answering them thanks to some aquatic helpers: tadpoles.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered genetic and biological mechanisms that enhance disease tolerance — the ability of cells and tissues to resist damage in the presence of invading pathogens — in developing tadpoles of Xenopus laevis frogs, and identified drugs that can keep the tadpoles alive even in the presence of lethal bacteria. Many of the same mechanisms are also found in mammals, 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 that we are having a harder and harder time killing. Our research has shown that focusing on modifying a host’s response to a pathogen rather than killing the pathogen itself could be an effective way to prevent death and disease without exacerbating the problem of antibiotic resistance,” said first author Megan Sperry, Ph.D., a Postdoctoral Fellow at the Wyss Institute who is co-mentored by Wyss faculty members Michael Levin, Ph.D. and Donald Ingber, M.D., Ph.D.

The research is published today in Advanced Science.

Mapping the tadpole tolerance network

The phenomenon of some hosts being tolerant of infectious pathogens that should sicken them has been well-documented in science over the last few decades. Mice, for example, can harbor pneumonia-causing Pneumococcus bacteria in their nasal passageswithout displaying signs of illness, and African and Asian monkeys are known to be less susceptible to certain pathogens than humans and our close ape relatives.

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