By studying the membrane protein FoxB in the hospital germ “Pseudomonas aeruginosa”, a research team from the Department of Chemistry at the University of Hamburg has discovered that it is involved in transporting iron from the environment into the bacteria. The findings could help target antibiotics more effectively to the cells of the germs and were published in the journal Proceedings of the National Academy of Sciences (PNAS).
Most microorganisms, such as bacteria, viruses and fungi, require iron to survive. However, its physicochemical properties make it difficult to dissolve, so it cannot be absorbed across membranes. Many bacterial species, as well as some fungi, are therefore able to form so-called siderophores, which are able to bind iron ions and keep them in a soluble state. Once such a complex is formed, the bound iron complexes can be taken up by the bacteria via the outer membrane. However, the subsequent path of the molecular complexes through the inner membrane of the bacteria differs in many species and is often not known in detail.
Scientists from the Department of Chemistry at the University of Hamburg have now analyzed the pathway of the molecular complexes in the rod bacterium Pseudomonas aeruginosa (P. aeruginosa). P. aeruginosa is a germ that occurs in moist environments such as showers, washbasins or ventilation tubes. It can survive in some disinfectants, is resistant to certain antibiotics, and is one of the most common hospital germs. The spectrum of illnesses caused by P. aeruginosa includes pneumonia, urinary tract infections, skin infections and eye infections.
For the study, the research team analyzed the structure of the membrane protein FoxB of P. aeruginosa and found that it is involved in the uptake of iron. Also assisting in the process was an artificial intelligence called AlphaFold2, developed by researchers at the British company DeepMind. It can precisely predict the structures of molecules and helped the Hamburg researchers decipher the structure and thus the function of FoxB.
“It has been shown that FoxB is not a transport protein, but a reductase. It reduces iron-III to iron-II so that it can then be taken up through the inner membrane.”
- Henning Tidow, professor in the Department of Chemistry at the University of Hamburg
The resolution of the structure, as well as the function, could also provide a new way to target antibiotics to the cells of bacteria: The research team’s structural studies, as well as previous work on transport across the outer membrane, have shown that the binding sites for the siderophore provide sufficient space to dock an antibiotic. This could then be transported through the membranes along with the complex and thus specifically taken up by the cells.
“This is definitely an approach we will pursue,” Tidow says. “The question is whether it can be cleaved back from the complex in the cell and stay there. Usually antibiotics go into cells well, but are quickly removed. That will be one of the challenges for us.”
