Iron metabolism and infection.
The review highlights the intrinsic problems in the acquisition of ferric iron (FeIII) by pathogenic microorganisms, and bacteria in particular, during their infection of animals. Acquisition of iron from host sources, such as ferritin, transferrin, and heme compounds, is discussed. Acquisition can be by direct contact, via a surface receptor protein of the bacterium, with one of the iron-containing compounds, but more frequently iron is acquired by the production of a siderophore. Over 500 different siderophores are now known; they work by having a superior binding power to that of the host iron-containing materials. They literally strip the iron out of these molecules. They are low-molecular-weight (< 1,000 Da) compounds that are produced in response to iron deprivation, which is a primary host defense mechanism against infections. The iron-siderophore complex is small enough to be taken up into the bacterial cells, usually via an active transport process; the iron is removed from the siderophore, normally by a reductive process, and is then incorporated into the various apoproteins of the bacterial cell or is stored within the bacteria in the form of bacterioferritin. To combat the effectiveness of the siderophores, animals may synthesize specific proteins to bind and nullify their action. The role of one such protein, siderocalin (= lipocalin 2), is discussed. However, these countermeasures have, in turn, been thwarted by at least one bacterium, Salmonella, glycosylating its siderophore (enterobactin/enterochelin) so that binding of the modified siderophore (now termed salmochelin) with lipocalin can no longer occur.
Ratledge
Colin
C
Department of Biological Sciences, University of Hull, United Kingdom. c.ratledge@hull.ac.uk
D001419:Bacteria / Q000378:metabolism* / Q000472:pathogenicity; D001424:Bacterial Infections / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism*; D011485:Protein Binding; D017262:Siderophores / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D002352:Carrier Proteins; D017262:Siderophores; D014168:Transferrin; D007501:Iron