Iron Acquisition from Transferrins by Campylobacter jejuni

Iron acquisition is vital for intestinal colonisation by Campylobacter jejuni. Characterisation of a number of iron uptake systems has occurred recently, allowing advancement in the understanding of the iron sources that C. jejuni utilises and how this occurs; however, the molecular basis of iron uptake from host iron-binding glycoproteins, the transferrins, is not known. The research presented here confirms that C. jejuni can use iron from the transferrins for growth and further characterises this process and the factors involved. Iron uptake from the transferrins requires proximity and appears to be receptor specific. Binding of lactoferrin to the cell surface is iron-responsive. Cj0178, a protein similar to TonB-dependent receptors, is required and the involvement of the enterochelin outer membrane receptor protein CfrA, FeoB, the ferrous iron inner membrane transporter, and the ABC transporter system Cj0175c-Cj0173c was also indicated. Less lactoferrin bound to cells without Cj0178 and complementation of the cj0178 mutation was successful. A role for Cj0178 in the uptake of haem was not demonstrated. Regulation of the genes cj0176c-cj0173c and cj0177-tonB1 was shown to require Fur and promoter activity levels increased under iron-restriction. The presence of two Fur-boxes indicated separate regulation of the operons. The catecholamine stress hormone noradrenaline augmented the growth of C. jejuni in the absence and presence of iron and in the presence of the transferrins, but was non-essential. A model is proposed of how transferrin-bound iron is used by C. jejuni. The process appears to be novel, involving a number of systems, but further work is required to confirm how they interact. The system through which noradrenaline may supply iron was investigated; however the mechanisms involved require further characterisation. The involvement of Cj0178 implies that the uptake of transferrin-derived iron is important for successful colonisation, which is vital for establishing an infection.