Catching BAM in the act: a strategy for novel antibiotics?

Gram negative bacteria are important pathogens to both humans and livestock responsible for life-threatening opportunistic systemic hospital infections, respiratory and urinary tract infections and gastric ulcers. As antibiotic resistance is emerging in the bacteria responsible for these conditions there is an urgent need to develop novel antibacterials on suitable targets. The beta-barrel associated machinery (BAM) complex of Gram negative bacteria which inserts outer membrane proteins in to this membrane is a promising novel target as it is vital for cell survival. In contrast to the wealth of structural and functional knowledge for BAM, its mechanism of action is still poorly understood, hindering rational drug design campaigns.
The aim of this project is to investigate BAM mechanism by using protein engineering methods (whose effects are will be validated using an in vivo survival assay) to test the different models proposed for BAM function. These insights will be used to trap a protein substrate with the ultimate aim of visualizing this complex using appropriate biophysical and structural methods.