Dissecting the role of a membrane-associated bacterioferritin complex in Neisseria gonorrhoeae

Bacterial infection is a fact of life. Antibiotics have considerably reduced mortality, but the spread of antibiotic resistance threatens to impede infectious disease control and compromise basic aspects of healthcare that we take for granted. In the UK ~44,000 deaths occur every year from untreatable bacterial infections, costing the NHS £2 billion annually.

Iron is a vital cofactor for many enzymes, and bacteria must ensure that they have an adequate supply of this essential nutrient. Upon infection by microorganisms, the animal host innate immune system typically reduces the availability of iron. In response, bacteria activate pathways for metal import, metal sparing, or metal storage to avoid stress from metal starvation. This competition for metals is termed "nutritional immunity". Ferritin proteins are the primary iron stores in all kingdoms of life, they act to oxidise and sequester iron in a bioavailable mineral form within a hollow protein cage. Some bacteria possess heme-binding bacterioferritins, which allow the rapid mobilisation of stored iron through electron transfer via the heme group.

This project will focus on the study of a membrane associated bacterioferritin complex from the Gram-negative pathogen Neisseria gonorrhoeae. This pathogen has been identified as a "superbug", with multiple strains and isolates that have become completely resistant to all last-line antibiotics. It is not surprising that this pathogen is listed by the Centre of Disease Control (USA), the World Health Organisation, and Public Health UK as a research priority.

Goals and Objectives:
Produce recombinant bacterioferritin complexes, for structural and functional analyses to understand how iron is stored within the compartment.
Use structural biology techniques, including X-ray crystallography and electron microscopy, to analyse the molecular structure of the bacterioferritin complex.
Make targeted gene knockouts in Neisseria gonorrhoea of the individual bacterioferritin components to understand their role in the physiology and pathogenicity of this bacterium.