Utilization of iron by Campylobacter jejuni
Iron is a nutrient that bacteria need for many essential processes in the cell. As part of the response to infection by bacteria, animals restrict the amount of iron available. In mammals lactoferrin (in mucosal secretions) and transferrin (in serum) tightly bind free iron to restrict its availability. Unfortunately, successful disease-causing bacteria have found ways to grab iron back from the host. The bacterial mechanisms involved in acquiring iron in the host usually consist of a specific pore on the outer surface of the bacterial cell and an associated transport system that makes the iron available inside the cell.
The most important food-associated bacterium that infects humans is Campylobacter and as such is responsible for much misery and economic loss in the UK. Campylobacter normally lives in the intestine of many animals, notably chickens, where they do not always cause disease. However, when humans eat food contaminated with campylobacters, an highly unpleasant cramping diarrhoea can follow. Food producers strive to minimise the risks of food poisoning for consumers, but if Campylobacter could be eliminated from the intestines of farm animals, particularly chickens, it would have a significant impact on human health by preventing many thousands of cases of food borne disease each year.
If control is to be achieved it is important that we better understand how Campylobacter colonises the intestine. Several components of campylobacters that are essential for growth in the intestine are involved in acquiring iron within the host. In our preliminary work, we have identified a system in campylobacters that can grab iron directly from lactoferrin and transferrin to support bacterial growth. This work has identified candidates for the specific pore on the outer surface of the bacterial cell and the associated transport system that moves the iron to the inside of the cell. Work by my colleague Julian Ketley, Department of Genetics, University of Leicester, aims to verify the identify of the components of the system and determine the methods by which iron is removed from lactoferrin/transferrin to allow bacterial growth. With a better understanding of the iron acquisition system we will be able to determine if it would be an suitable target for intervention on the farm in order to block growth in the animal gut and reduce food contamination.
Utilization of lactoferrin-bound and transferrin-bound iron by Campylobacter jejuni. J Bacteriol. 2008 190:1900-11
Campylobacter jejuni NCTC 11168 was capable of growth to levels comparable with FeSO4 in defined iron-limited medium (minimal essential medium alpha [MEMalpha]) containing ferrilactoferrin, ferritransferrin, or ferri-ovotransferrin. Iron was internalized in a contact-dependent manner, with 94% of cell-associated radioactivity from either 55Fe-loaded transferrin or lactoferrin associated with the soluble cell fraction. Partitioning the iron source away from bacteria significantly decreased cellular growth. Excess cold transferrin or lactoferrin in cultures containing 55Fe-loaded transferrin or lactoferrin resulted in reduced levels of 55Fe uptake. Growth of C. jejuni in the presence of ferri- and an excess of apoprotein reduced overall levels of growth. Following incubation of cells in the presence of ferrilactoferrin, lactoferrin became associated with the cell surface; binding levels were higher after growth under iron limitation. A strain carrying a mutation in the cj0178 gene from the iron uptake system Cj0173c-Cj0178 demonstrated significantly reduced growth promotion in the presence of ferrilactoferrin in MEMalpha compared to wild type but was not affected in the presence of heme. Moreover, this mutant acquired less 55Fe than wild type when incubated with 55Fe-loaded protein and bound less lactoferrin. Complementation restored the wild-type phenotype when cells were grown with ferrilactoferrin. A mutant in the ABC transporter system permease gene (cj0174c) showed a small but significant growth reduction. The cj0176c-cj0177 intergenic region contains two separate Fur-regulated iron-repressible promoters. This is the first demonstration that C. jejuni is capable of acquiring iron from members of the transferrin protein family, and our data indicate a role for Cj0178 in this process.
Related:
- Campylobacter jejuni
- How Campylobacter jejuni survives within cells
- Protein promotes antibiotic resistance in Campylobacter
Tags: Bacteria, Biology, Food, Genetics, Health, Microbiology, Science, University of Leicester
