Developing new routes to antibiotic discovery in Streptomyces species
Lead Research Organisation:
University of East Anglia
Department Name: Graduate Office
Abstract
Most antibiotics in clinical use are made by soil bacteria called Streptomyces and were discovered between 1940 and 1960. Misuse of antibiotics over the last 60 years has led to widespread resistance and now some life-threatening infections can no longer be treated. The O'Neil report on AntiMicrobial Resistance predicts that it will be the major cause of death (10M a year, worldwide) by 2050 and recommends stimulating early stage antibiotic discovery.
This project is focussed on understanding and exploiting the signalling pathways which control antibiotic production in Streptomyces species. They only make ~10% of their antibiotics under lab conditions and the rest are 'cryptic' which means they are made in nature but not in the lab. If we can understand and manipulate the signalling pathways that control their production we can discover many new antibiotics. Antibiotic production is linked to sporulation and we have identified a master regulator called MtrA which coordinates these processes. Activating MtrA switches on cryptic antibiotics, most likely by switching on other regulators that control the life cycle. This project will investigate the role of WblE, a regulator which is controlled by MtrA and is essential for survival. WblE contains an iron-sulfur cluster and likely senses the gas nitric oxide (NO), which is an important biological signalling molecule. NO inhibits sporulation and activates antibiotic production in Streptomyces and we predict it does this via WblE.
This project is focussed on understanding and exploiting the signalling pathways which control antibiotic production in Streptomyces species. They only make ~10% of their antibiotics under lab conditions and the rest are 'cryptic' which means they are made in nature but not in the lab. If we can understand and manipulate the signalling pathways that control their production we can discover many new antibiotics. Antibiotic production is linked to sporulation and we have identified a master regulator called MtrA which coordinates these processes. Activating MtrA switches on cryptic antibiotics, most likely by switching on other regulators that control the life cycle. This project will investigate the role of WblE, a regulator which is controlled by MtrA and is essential for survival. WblE contains an iron-sulfur cluster and likely senses the gas nitric oxide (NO), which is an important biological signalling molecule. NO inhibits sporulation and activates antibiotic production in Streptomyces and we predict it does this via WblE.
