The transfer of Fe from host proteins to pathogenic bacteria
Free iron is scarce in the body and the limited availability of this essential element may be an effective form of innate immunity to infection. Consequently, systems to acquire iron from the host are important virulence factors in pathogenic microorganisms. Haem proteins form the largest reservoir of iron in the body, with haemoglobin (Hb) accounting for ~ 70% of total iron. Hence, it is not surprising that many pathogenic organisms have acquired receptors for binding and stripping iron from Hb. Despite the importance of this mechanism, the structural basis for Hb recognition and haem/iron extraction is poorly understood.
In this project we are characterizing putative Hb receptors from common bacterial pathogens such as Streptococcus pyogenes, Staphylococcus aureus and Porphyromonas aeruginosa. In many cases, the genes for multiple iron-acquisition proteins are arranged in an operon structure, but the precise roles in Hb binding and haem/iron extraction have not been determined. We aim to characterise such proteins at the biochemical, structural and functional levels. In this way we hope to identify targets through which to inhibit bacterial growth by blocking Fe uptake. Of particular interest to our group are the mechanisms by which the structure of Hb is disrupted in order to remove the haem/Fe group.
- Dr David Gell (Member)
- Kaavya Krishna Kumar (PhD Candidate)