Iron acquisition from host molecules by campylobacter jejuni
thesisposted on 15.12.2014, 10:38 by Jonathan D. Rock
The ability of pathogenic organisms to obtain iron in the host is critical for pathogenesis. Limited research has been carried out into iron acquisition from host molecules by the important gastro-intestinal pathogen Campylobacter jejuni. The objective of this study was to investigate the ability of C. jejuni to acquire iron from host molecules and the nature of iron responsive regulation of gene expression in C. jejuni. Four C. jejuni genes encoding putative haem uptake proteins are arranged in a predicted operon. Data presented in this study confirms that ChuA, a protein similar to haem receptors, functions as an outer membrane haem receptor in C. jejuni and is expressed from a promoter in the region upstream of chuA, under iron-responsive control by Fur. The chuB, C and D genes are non-essential for iron acquisition from haem, however involvement of chuB, C and D in haem uptake cannot be dismissed due to the possible complementation of chu mutation by another system. Identification of alternative haem uptake systems in C. jejuni was unsuccessful. For the first time it was demonstrated that C. jejuni can acquire iron from both transferrin (Tf) and lactoferrin (Lf) in a contact dependent, substrate specific manner which does not require noradrenaline. Iron acquired from Tf and Lf accumulates in the soluble cellular fractions and is utilised for cellular growth. The molecular basis of iron acquisition from Tf or Lf has not been elucidated. C. jejuni fur is co-transcribed with the lysS and glyA housekeeping genes from two distal promoters (adjacent to the gatC and Cj0399 genes). Expression from either promoter is not controlled by Fur in response to iron and therefore is not autoregulated. This study demonstrates the presence of several sytems involved in iron acquisition from host molecules. Future research is essential to investigate the importance of these systems during host colonisation.