Small peptides as potential antibiotics

Small peptides attack bacteria in many different ways and may well become a new generation of antibiotics. Biologists at the Ruhr-Universität Bochum (RUB) have been researching how such peptides kill bacterial cells.

"It is quite possible that, in ten years time, all of the currently marketed antibiotics will lose their power, because bacteria will have become resistant against all active agents," says Junior Professor Dr Julia Bandow. Consequently, it is high time to develop new antibacterial drugs. Together with colleagues from Germany, Austria, and Canada, she reports on the peptide's mode of action in the journal PNAS.

The team of Julia Bandow, who heads the RUB's Junior Research Group Microbial Antibiotic Research, has been studying the MP196 peptide as a representative of a group of very small positively charged peptides that consist of some four to ten amino acids. Earlier studies had shown that MP196 is efficient against various bacteria, including particularly problematic multi-resistant pathogens that frequently cause sepsis. How MP196 kills bacteria remained unclear. However, in order for a new substance to be approved as a drug, its mechanism of action has to be fully understood.

The biologists have closed this gap. They showed that the MP196 peptide integrates into the bacterial cell membrane. In doing so, it delocalises proteins localised at the bacterial cell membrane that participate in vital processes. Two processes in particular are severely affected: MP196 disrupts the biosynthesis of the cell wall, i.e. of the outer envelope that encloses the cell membrane and provides physical stability. It also inhibits cell respiration and, consequently, the production of the energy-storing molecule ATP. This results in cellular energy deficiency, thus preventing the synthesis of macromolecules vital for bacterial growth.