A previously unknown mechanism used by the body to prevent wound infections has been discovered by team of researchers from A*STAR, Lund University, Nanyang Technological University, and Copenhagen University1. This finding could provide scientists with a new way to fight infection, a critical development when many microbes are becoming increasingly resistant to antibiotics.
Skin wounds are open doors for bacteria to enter the body and cause infections. The body uses a range of different strategies to protect itself against this threat, including blood clotting and immune responses. In a surprising find, Jitka Petrlova at Lund University, Sweden, together with Peter Bond’s team at the A*STAR Bioinformatics Institute, has discovered a strategy that the body uses to neutralize invading microbes.
Using an impressive array of techniques, including biophysical, biochemical, and microbiological methods, fluorescence and electron microscopy, and computer modeling, Petrlova and her team discovered that an enzyme secreted by immune cells such as neutrophils and macrophages cuts up thrombin, an enzyme that plays an important role in blood clotting, into fragments . These thrombin fragments then collect bacteria and their toxins together. This occurs rapidly in a wound, and the invaders are gobbled up by inflammatory cells. This phenomenon was not seen in normal blood plasma; it was observed only in wounds.
The discovery suggests a new approach for fighting bacteria. “Perhaps, we don’t need to kill bacteria with antibiotics. Instead, we could simply gather them together and give the body a helping hand in combating infection,” says Petrlova. “We believe this to be a fundamental mechanism for taking care of both bacteria and their toxins during wound healing.”
Petrlova says: “Nature has effectively created different defense mechanisms, and wound healing provides a rich source of new discoveries. The ability to effectively heal wounds is of evolutionary significance to our survival. Compared to antibiotics, innate immunity has been around for millions of years, and we should consider the application of these concepts in an era of increasing antibiotic resistance.”
The team’s finding could also have implications for diseases such as Alzheimer’s and Parkinson’s. “Various aggregating proteins can cause amyloid diseases in the skin or internal organs such as the brain,” says Petrlova. “Such degenerative diseases could be caused by over-activation of a mechanism that is supposed to protect us from infections.”
The A*STAR-affiliated researchers contributing to this research are from the Bioinformatics Institute. For more information about the team’s research, please visit the Multiscale Simulation, Modeling and Design webpage.
- Petrlova, J., Hansen, F. C., van der Plas, M. J. A., Huber, R. G., Mörgelin, M. et al. Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism. Proceedings of the National Academy of Sciences USA 114, E4213–E4222 (2017).| Article