Scientists have discovered a protein that enables bacteria to shut down into dormant spores under extreme conditions. The process, which enables the bacteria to become practically indestructible, explains why bacteria can survive in uninhabitable places such as under the permafrost, in the depths of the ocean or in outer space.
This ability to sporulate, known as sporulation, also enables superbugs to evade hospital cleaning and then come back to life in the guts of compromised patients.
By discovering a new protein involved in sporulation in a group of bacteria, scientists hope it could deepen our understanding of bacteria’s ability to survive against the odds, and even open up new avenues for antimicrobial therapies.
The study, covered in two separate papers published in Genes and Development today, looks at Bacillus — a group of bacteria including cereus, which is responsible for food poisoning, and anthrax. The research team included scientists from the Department of Chemistry, King’s College London, the University of California San Diego, the Max Planck Unit for the Science of Pathogens in Berlin, and Mount Holyoke College in the USA.
Professor Rivka Isaacson, co-author of the papers, said: “We have known for a long time that bacteria are able to perform metabolic shut-down in unfavourable environments, transforming into long-lived, indestructible dormant spores which can survive for thousands of years.”
“This happens through asymmetrical cell division, where the bigger part — the ‘mother cell’ — engulfs the smaller part, the ‘forespore’, providing it with nutrients and a protective outer layer. It continues to build up protective layers around its genetic materials until it is ready to be released as a spore.”
Whilst this process is well understood, the mechanisms behind shutting down metabolism have remained a mystery until the scientists discovered a previously uncharacterised protein called MdfA was behind it.
Professor Isaacson explained: “Every cell has a ‘recycling centre’ called a protease, responsible for breaking down old or damaged proteins. We discovered that MdfA — a protein we didn’t know the function of previously, acts as an adaptor that recruits the proteins for recycling.
“In the case of sporulation, this protein instructs the cell to get rid of its metabolic enzymes responsible for active growth, by destruction through the protease, thereby effecting the metabolic shutdown part of sporulation.”
Once MdfA had been identified, chemists at King’s were able to solve the crystal structure of the protein using x-ray crystallography, revealing a completely new molecular shape. This has enabled them to further understand how MdfA binds to a part of the recycling chute in cells, a protein called ClpC.
The scientists also found that when they forced happily growing cells to overexpress MdfA, it became toxic to the cells and they burst.
Whilst MdfA isn’t present in most other forms of bacteria, ClpC and the recycling machine is, so similar proteins may be behind sporulation in other bacteria, including those that cause disease.
Professor Isaacson said: “This discovery has improved our understanding of how bacteria operate and opens up a new way of exploring sporulation. Given that sporulation plays a key part in bacteria’s survival, the more we understand this process, the more we will be able to control and eliminate harmful bacteria.”
The scientists also hope their findings might lead to new strategies for developing antimicrobials.
Professor Isaacson added: “If you can target the cell degradation machinery to remove particular proteins, this can open new avenues for anti-microbial therapies, similar to an emerging form of cancer treatment, known as targeted protein degradation or PROTAC, which repurposes a cell’s recycling system for therapy.”
