Harvard Medical School researchers have discovered a new type of cellular sensor that helps dormant bacteria detect the presence of environmental nutrients and quickly become active again. These sensors were found to double as channels through the membrane that remain closed during dormancy but rapidly open when they detect nutrients. Electrically charged ions can then flow out of the cell membrane, causing the shedding of protective spore layers and the activation of metabolic processes after years, or even centuries, of dormancy.
These findings, published in Science, solve a riddle stumping biologists for more than a century and could inform the design of methods preventing dangerous bacterial spores from causing outbreaks.
Some bacteria enter dormancy and become spores to survive unfavorable environmental conditions. In doing so, all biological processes are put on hold and layers of protective armor are generated around the cell. These dormant cells allow bacteria to wait out periods of famine and shield themselves from the effects of extreme heat, dry spells, UV radiation, harsh chemicals, and antibiotics.
For over a century, scientists have known that when the spores detect nutrients in their environment, they rapidly shed their protective layers and reignite their metabolic engines. While the sensor enabling them to detect nutrients was discovered almost 50 years ago, the means of delivering the “wake-up” signal and how it triggers bacterial revival remained unclear.
In this study, the researchers found that the nutrient sensor itself assembles into a conduit that opens the cell back up for business. In response to nutrients, the membrane channel opens, allowing ions to escape from the spore’s interior. This initiates a chemical cascade allowing the dormant cell to shed its protective armor and resume growth.
The scientists used multiple strategies to answer their research questions, including artificial intelligence tools used to predict the structure of the intricately folded sensor complex, a structure made of five copies of the same sensor protein. Additionally, the team applied machine learning to identify interactions between subunits that make up the channel.
Throughout the study, the scientists made several surprising observations that confused them. In this case, senior author David Rudner, professor of microbiology at the Blavatnik Institute at HMS, described the discovery process as a series of confounding observations that slowly took shape.
With this discovery, scientists now know how bacteria sense environmental changes and take action to break out of dormancy when their systems are almost completely shut down inside a protective casing.