Bacterial polyamines - from curiosity to antimicrobial target?

Antimicrobial resistant (AMR) pathogens are one of the greatest threats to human health. When considering the development of novel therapies against these pathogens it is imperative to increase our understanding of the molecular basis of pathogenesis in these bacteria. Enzymatic pathways specific to bacteria, that are required for virulence, may present potential targets for the design of novel drugs. This project will investigate the roles of polyamines (particularly 1,3-diaminopropane) as regulators of virulence in two increasingly important AMR bacteria: Klebsiella pneumoniae and Acinetobacter baumannii (for which there is evidence that 1,3-diaminopropane is required for virulence). A multi-disciplinary approach will be taken, with full training in a wide variety of techniques.
The student will be primarily based in the molecular bacteriology lab of Dr Laura Hobley (Nottingham) where the work will focus on investigating the roles of 1,3-diaminopropane synthesis on regulating processes in the two pathogens, particularly those involved in virulence. In the protein/enzyme biochemistry lab of Dr Andrew Lovering (Birmingham) the student will study the enzyme structures and screen for putative inhibitory molecules. These potential inhibitors will then be assayed for activity when applied to the bacteria and checked for any therapeutic effects in several laboratory models of pathogenesis.