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27 / 09 / 2018

Regulation of formicamycin biosynthesis: new potent antibiotics against MRSA (HUTCHINGS_U19DTP)

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Most antibiotics in clinical use today are based on microbial natural products that were discovered during a golden age of antibiotic discovery that peaked in the mid 1950s. Remarkably, one genus of soil bacteria, called Streptomyces, account for 55% of clinically used antibiotics. The discovery pipeline dried up in the 1960s because scientists began to rediscover the same microbial strains making the same antibiotics and assumed they had found them all. However, genome sequencing from 2000 onwards has revealed these bacteria encode thousands of novel molecules that have not yet been isolated. We isolate new species of Streptomyces from under-explored, symbiotic niches such as the nests of fungus-growing ants, sequence their genomes and then engineer them using CRISPR to activate biosynthetic gene clusters encoding novel molecules. This project focusses on a new species we isolated called Streptomyces formicae which makes novel antibiotics called formicamycins that are potent against multidrug resistant human pathogens such as MRSA and vancomycin resistant enterococci. The project is aimed understanding the regulation of formicamycin biosynthesis with a view to making over-producing strains so the molecules can be further characterised as potential clinical leads. We will also determine the natural resistance mechanisms in S. formicae and do experiments to see if these natural resistance genes can confer resistance on pathogenic bacteria. This is important for assessing the potential of these new antibiotics to be used as drugs. The PhD will be co-supervised by Matt Hutchings, a microbiologist at UEA, and Barrie Wilkinson, a natural products chemist at JIC, both on the Norwich Research Park.