Discovery from Collaboration between Harvard's Wyss Institute and Boston University Provides Deep Insights into Complexity of Bacterial Strains and Antibiotic Resistance
BOSTON, Mass. — Researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard and from Boston University have discovered that charitable behavior exists in one of the most microscopic forms of life — bacteria. Their findings appear in the current issue of Nature.
In studying the development of antibiotic-resistant strains of bacteria, the researchers found that the populations most adept at withstanding doses of antibiotics are those in which a few highly resistant isolates sacrifice their own well being to improve the group’s overall chance of survival.
This bacterial altruism results when the most resistant isolates produce a small molecule called indole. Indole acts as something of a steroid, helping the strain’s more vulnerable members bulk up enough to fight off the antibiotic onslaught. But while indole may save the group, its production takes a toll on the fitness level of the individual isolates that produce it.
"We weren’t expecting to find this," said lead investigator James J. Collins, Ph.D., professor of Biomedical Engineering at Boston University, a core faculty member of the Wyss Institute, and a Howard Hughes Medical Institute investigator. "Typically, you would expect only the resistant strains to survive, with the susceptible ones dying off in the face of antibiotic stress. We were quite surprised to find the weak strains not only surviving, but thriving."
The findings also shed new light on the level of complexity and heterogeneity within bacterial strains. Until now, it was assumed that the overall resistance level of any given population was reflected in each of its isolates. Instead, Collins and his team found that dramatic differences can exist within a single population with some bacteria showing exceptional resistance and some almost none, not unlike cancer cells in humans.
The fact that the full complexity of bacteria strains can now be more accurately understood has significant ramifications for the medical community. "Now, when we measure the resistance in a population, we’ll know that it may be tricking us," said Collins. "We’ll know that even an isolate that shows no resistance can put up a stronger battle against antibiotics thanks to its buddies."
Collins is a founder of the field of synthetic biology, an area of research that combines science and engineering to construct new biological circuits that can reprogram organisms, particularly bacteria, to perform desired tasks, much like we program computers now.
His research at Boston University has also led to the development of a new class of medical devices being developed at the Wyss Institute, including vibrating insoles that help reduce falls among elderly users and normalize the gait of children with cerebral palsy.
"The Wyss Institute was founded on the premise that by breaking down institutional barriers and bringing together some of the world’s top minds in science and engineering, we could accelerate transformative discovery," said Donald E. Ingber, M.D., Ph.D., Founding Director of the Wyss Institute. "I’m proud to say that the research being done by Dr. Collins is a great example of how this vision is beginning to play out."