ABSTRACT
A major environmental signal for invading pathogens is the extremely low availability of iron in mammalian tissue fluids. Normal body fluids contain high-affinity, iron-binding glycoproteins, transferrin or lactoferrin, or both. These proteins bind iron extremely tightly and ensure that no free iron is available to invading pathogens. Bacteria that multiply under these conditions to establish an infection are able to adapt to this iron-restricted environment and express mechanisms for assimilating protein-bound iron, or for acquiring it from liberated hemoglobin or heme. The ability to grow pathogenic bacteria under iron-restricted conditions is an essential step toward being able to study the metabolism of such bacteria as they multiply in vivo during infection. Growth of bacteria in an iron-restricted environment can result in considerable phenotypic changes. The best understood iron-uptake system employed is that known as siderophore-mediated iron uptake, in which the bacteria, in response to iron restriction, secrete soluble, low molecular weight, high-affinity iron-chelating compounds known as siderophores.
