Greg Challis

Discovery, biosynthesis and bioengineering of antibiotics from Gram-negative bacteria

The overwhelming majority of antibiotics in clinical use are derived from natural products isolated from Gram-positive Actinobacteria. Pathogenic microorganisms are becoming increasingly resistant to these compounds, and there is an urgent need to discover novel antibiotics to address the emerging health threat this poses. In contrast to Actinobacteria, the potential of Gram-negative bacteria to produce antibiotics has been relatively underexplored. In this lecture, the discovery of antibiotics from Burkolderia and other Gram-negative bacterial genera, with activity against drug resistant strains of Mycobacterium tuberculosis and Acinetobacter baumannii, will be presented. Efforts to understand the biosynthesis of these metabolites will be discussed and application of the knowledge gained to bioengineer the production of novel analogues with enhanced bioactivity will be described.