Trapping multidrug-resistant bacteria in molecular glue

Trapping multidrug-resistant bacteria in molecular glue
With multidrug-resistant bacteria and antibiotic resistance on the rise worldwide, new drugs are urgently needed. © World Bank Photo Collection - Flickr CC BY-NC-ND 2.0

Researchers at VIB, KU Leuven and UZ Leuven, Belgium, have devised an innovative approach to develop antibacterial drugs. With multidrug-resistant bacteria and antibiotic resistance on the rise worldwide, new drugs are urgently needed.

Flemish biotech spin-off Aelin Therapeutics will exploit this new technology to produce new antibiotics for the clinic. Experts now agree that unless we discover new medicines soon, the post-antibiotic era may be upon us as multidrug-resistant bacteria are constantly on the rise, effectively pushing human healthcare back to the 1940s.

Currently most antibiotics that we know work according to only a few mechanisms of action, and so when a bacterium becomes tolerant to one drug, it often becomes tolerant to the whole family, thus making it a multidrug-resistant bacterium.

This suggests that an entirely new class of drugs that shares no structural or mechanistic similarities with the existing antibiotics is necessary.

Professors Joost Schymkowitz and Frederic Rousseau of VIB-KU Leuven in collaboration with Professor Johan Van Eldere of University Hospitals Leuven have developed a new way of designing antibiotic drugs that can give rise to many new antibacterial molecules.

What do the new drugs do?

The new drugs penetrate bacterial cells where they induce a process called protein aggregation. Proteins that normally need to carry out essential functions for the bacteria – such as digesting their food – clump together and can no longer carry out their work. As this affects many proteins in the bacterial cell all at once, the bacteria rapidly succumb and die.

In a recent Nature Communications publication, the scientists reveal novel molecules with a strong antibacterial (bactericidal) activity against Gram-negative bacteria.

The technology will now be further explored and exploited by the Flemish start-up Aelin Therapeutics. Founded last December after attracting €27m in investments, this biotech company uses the protein aggregation approach (PeptinTM-technology) devised by Schymkowitz and Rousseau to develop new therapeutics.

Via Aelin Therapeutics the lab findings will be applied to generate many more antibacterial molecules. The company aims to apply the same technology to target a wide array of other diseases.

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