Researchers at Durham have helped unlock new understanding of how bacteria import antimicrobial peptides - the molecules that can kill or inhibit microbes.
Their discovery could inform the development of future antibacterial therapies.
Scientists from our Centre for Programmable Biological Matter (CPBM) contributed to the international study. The research sheds new light on SbmA, a key transporter protein found in the membranes of bacteria such as E. coli.
Bacterial cells are surrounded by a protective membrane, which controls what can enter and leave the cell.
SbmA is one of the transporters embedded in this membrane and plays a crucial role in allowing antimicrobial peptides to cross this barrier.
SbmA functions a little like a two‑way door. It opens on the outside of the membrane to capture a peptide and then opens on the inside to release it into the cell.
Understanding how this process works in detail is scientifically and medically important. Particularly as researchers explore new ways of exploiting natural uptake pathways to develop novel antibacterial treatments.
Earlier research had already captured the structure of SbmA with its “outer door” open.
This new study goes further by using advanced structural approaches to identify several new structures of SbmA, including forms in which the “inner door” is open.
Together, these snapshots reveal how the transporter flips between different states to move antimicrobial peptides across the bacterial membrane.
A clearer picture of how SbmA works could help scientists design antimicrobial peptides and peptide‑based drugs that enter bacteria more efficiently.
The findings may also support the development of delivery systems that use SbmA to transport therapeutic molecules directly into bacterial cells.
By pinpointing structural features that are essential for SbmA’s function, the research could inform strategies to limit or overcome bacterial resistance.
In the longer term, these insights may even open up possibilities for engineering SbmA‑like systems for use in biotechnology and synthetic biology.
Durham researchers Dr Piotr Stępień and Professor Jonathan Heddle contributed to the study as part of a wide‑ranging international collaboration.
The project involved senior research groups from Imperial College London, the University of Groningen, Jagiellonian University, the Medical University of Vienna, the University of Manchester, the University of Oxford, the University of Leeds, the University of St Andrews, the Rutherford Appleton Laboratory, and Kyoto University.
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