Research reveals how bacteria hijacks proteins to transport antibacterial peptides

Bacterial species are under continuous warfare with each other for access to nutrients. To gain an advantage in this struggle, they produce antibacterial compounds that target and kill closely related species. Now, researchers led by the Research Complex’s Dr. Konstantinos Beis from Imperial College London, together with Professor Jonathan Heddle from Jagiellonian University, Krakow, have uncovered the mechanism of one of bacteria’s attack tactics.

The team imaged in detail the structure of a protein called SbmA, that bacteria like E. Coli use to take in peptides. Other bacteria can ‘hijack’ SbMA by letting it take in peptides that have antibiotic properties, which can in turn harm their bacterial rivals. To establish the molecular mechanism of the peptides as they move, their structure was examined using cryo-EM techniques at Polish national cryo-EM facility SOLARIS and the UK’s national electron bio-imaging centre eBIC at Diamond Light Source. The structural organization of SbmA has not been observed in secondary transporters before and the structure revealed a novel fold, defining a new class of SbmA-like peptide transporters.

In a new paper published today in Science Advances, the team demonstrates how SbmA is hijacked at the molecular level, which could pave the way for designing new antibiotics that take advantage of this new discovery. This new structure also reveals new insights into how such transporters are powered, potentially bridging the gap between proton-driven and ATP-driven transporters.

This new research by Imperial, Jagiellonian University, Research Complex, eBIC and Diamond highlights how collaboration is key to making strides in research and the combined efforts and close proximity of our facilities to allow studies to be accelerated with ease and accuracy.

Dr. Beis says,

The preparation of the SbmA and BacA protein samples for structural and functional work have greatly been facilitated by access to state-of-the-art laboratories at RCaH where Konstantinos Beis lab is based. Access to cryo-EM microscopes at SOLARIS and eBIC gave us the edge on determining the high resolution structure of these novel transporters.

The paper has also inspired the journal issue’s front cover (Science Advances, Vol 7. Issue 37, 10th Sept 2021) as described below:

ONLINE COVER: Evoking the mystery of nature, this image features a Jeff Koons–inspired representation of the SbmA transporter structure. The ice block represents the cryo-electron microscopy used to determine the structure. By unraveling the protein structure, Ghilarov et al. were able to establish the molecular mechanism behind bacteria’s sensitivity to certain antibiotics. This research could aid in designing new antibacterial agents.

Read the full paper in Science Advances: ‘Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides’.

Image: Alina Kurokhtina/Dmitry Ghilarov