Antibiotics have truly revolutionized our medical practice. They have become indispensable in modern medicine as they are essential to combat life-threatening infectious diseases. However, a major threat to healthcare is rising as bacteria develop resistance mechanisms to escape the effects of antibiotics.
In addition to the direct risk of inability to treat routine infections, resistant microbes also pose a considerable risk to complex surgeries, e.g. joint replacements and organ transplants, chemotherapy and chronic diseases, as these rely on the effectiveness of antibiotics. It is predicted that if no direct action is taken, antimicrobial resistance will cause 10 million deaths each year by 2050, which is more than cancer currently does. In order to combat the resistance problem, the discovery of new antibiotics is urgently needed.
We have previously scrutinised libraries of synthetic small molecules leading to the discovery of promising lead compounds for novel antibiotics (see references below). In addition, microbial natural products, from which the vast majority of existing antibiotic agents have been derived, offer an enormous reservoir of novel potential antibacterial compounds. However, the biosynthetic gene clusters encoding these natural product pipelines are usually silent in standard lab conditions or the clusters reside in uncultivatable bacteria. The challenge consists of unlocking these cryptic clusters and making their products available to test their antibacterial activity.
To tackle this challenge, the possibilities of droplet microfluidics are exploited in our group. This technology allows high-throughput screening on single-cell level and efficient, automatic sorting of the interesting droplets. Combined with cutting-edge bio-engineering tools, we aim to access the wide diversity of uncharacterized natural products, which will lead to the discovery of new antibiotics.
(A) Mask design of the glass-silicon microfluidic chip for generating droplets. (B) Droplet generation and storage on-chip in the 0.2 μl cavity. (C) Growth of E. coli cells expressing GFP in droplets (left: brightfield; right: fluorescence).
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