Discovering novel antibiotics from Streptomyces

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Natural products (NPs) from Streptomyces bacteria and their close relatives account for two thirds of the antibiotics currently used in human medicine but no new classes of antibiotic have been discovered since the 1980s. The UK Prime Minister David Cameron recently acknowledged that the shortage of new antibiotics threatens to take medicine back to the dark ages and the search for new antibiotics is now a global health priority.For the last six years we have been searching for novel antibiotic-producing strains of bacteria in the nests of fungus growing (leafcutter) ants which live in South and Central America. This is an environmental niche that has not been explored before and it offers good prospects for the discovery of novel strains and antibiotics. The ants cut leaves to feed to a symbiotic fungus which they grow for food and they grow antibiotic-producing bacteria on their bodies to protect themselves and their fungus against infections. The team has isolated > 400 strains of antibiotic-producing bacteria and started to characterise some of these strains in detail. One such strain is a new species of Streptomyces that produces at least two new classes of NP with novel chemical scaffolds. Analysis of the complete genome sequence of this strain suggests it makes several more novel NPs. In this project the successful applicant will use a combination of genome analysis, activity guided fractionation and natural products chemistry to characterise the novel NPs made by this Streptomyces strain and to identify the biosynthetic pathways and encoding gene clusters for each of these compounds. Novel NPs will be screened against multidrug resistant bacteria and fungi to identify lead compounds that may be useful in human medicine.