Trapping multidrug-resistant bacteria in molecular glue

February 28, 2018, VIB (the Flanders Institute for Biotechnology)
Credit: CC0 Public Domain

Researchers at VIB, KU Leuven and UZ Leuven have devised a novel approach to develop antibacterial drugs. With antibiotic resistance on the rise worldwide, such new drugs are urgently needed. The Flemish biotech spin-off Aelin Therapeutics will exploit the technology to produce new antibiotics for the clinic.

Around the world are developing new strategies that render them resistant to , resulting in an increasing number of patients dying from untreatable infections. Experts now agree that unless we discover new medicines soon, the post-antibiotic era may be upon us, effectively pushing human healthcare back to the 1940s. In particular, a class of bacteria called 'Gram-negative bacteria', which include the well-known species E. coli, are causing major problems in our hospitals.

The problem is that most antibiotics that we know today 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. What we need to solve this situation is an entirely new class of drugs that shares no structural or mechanistic similarities with the existing antibiotics.

Prof. Joost Schymkowitz and Prof. Frederic Rousseau of VIB-KU Leuven in collaboration with Prof. Johan Van Eldere of University Hospitals Leuven have gone one step further: they have developed a new way of designing antibiotic drugs that can give rise to many new antibacterial molecules.

These drugs penetrate bacterial cells where they induce a process called protein aggregation. This process resembles what happens when boiling an egg, but now without heat: 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 publication in the highly regarded scientific journal Nature Communications, 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 27 million Euro 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.

Explore further: Antibacterial applications of graphene oxides

More information: Ladan Khodaparast et al. Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis, Nature Communications (2018). DOI: 10.1038/s41467-018-03131-0

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