Pseudomonas aeruginosa is a ubiquitous environmental bacterium, best known as an opportunistic human pathogen. It can cause several infections, manly in immunocompromised patients, and is also associated with persistent respiratory infections in patients with cystic fibrosis (CF). As in many bacterial species, the expression of genes in Pseudomonas aeruginosa is controlled by sigma factor (σ factor) proteins, such as members of the extra-cytoplasmic functions (ECF) sigma factor family. There is also a group of alternative σ factors which are activated under environmental conditions and are able to control the expression of genes involved in functions such as virulence, stress response and iron uptake, amongst others.

In humans iron is generally sequestered intracellularly in heme-containing compounds or in fluids by iron-binding proteins such as lactoferrin and transferrin. As almost all pathogenic organisms need iron for survival, bacteria such as P. aeruginosa overcome the problem by the synthesis of siderophores such as pyoverdine which enables the acquisition of iron required for in vivo growth and pathogenesis. It is believed that in P. aeruginosa the activities of the ECF sigma factors. fpvI and pvds are controlled by the fpvR, anti-sigma factor. During the process pvdS is responsible for the biosynthesis of pyoverdine while fpvI is responsible for the expression of its receptor namely the fpvA protein.^1 2 3 4 

The aim of this project is to overexpress and purify the sigma factors involved in the pyoverdine-mediated acquisition of iron by P. aeruginosa (fpvI and pvdS) and to characterise their structures in complex with domains of the anti-sigma factor fpvR. Progress toward that aim will be described.