Project: Broad Spectrum Antibiotic Discovery
Research group: Hlouchová
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Deadline is closed
There remains a need for novel antibiotics, particularly those directed against multi-resistant Gram-negative bacteria. Common species of the genera Acinetobacter, Pseudomonas and many Enterobacteriaceae are currently resistant to all known antibiotics. Unless antibacterial development is re-energized, there is a risk that a growing proportion of hospital infections become effectively untreatable.
A high throughput search is proposed for the discovery of novel broad-spectrum antibiotics. The screen will use large libraries of synthetic peptides to target bacterial ribosomal assembly and function. The binding sites of most widely used antibiotics are concentrated at and around functional hot spots of the small 30S and the large 50S subunit of the bacterial ribosome. These sites are often dominated by elements of the rRNA but still require protein activity. The libraries will be formed from mutated variants of natural ribosomal proteins necessary for the formation and activity of both the small and the large ribosomal subunit. The mutation strategy involves an increased likelihood of binding to the ribosome target, loss of function mutations.
The outcome of the project is the expected discovery of novel antibiotics leads, which target by design, gram negative, resistant and otherwise difficult to treat microbes.
Deadline is closed