Staphylococcus aureus causes a significant amount of human morbidity and mortality. The ability of S. aureus to cause disease is dependent upon its acquisition of iron from the host. S. aureus can obtain iron from various sources during infection, including heme and transferrin. The most abundant iron source in humans is heme-iron bound by hemoglobin contained within erythrocytes. S. aureus is known to lyse erythrocytes through secretion of pore-forming toxins, providing access to host hemoglobin.

Proteins of the iron-regulated surface determinant (Isd) system bind host hemoproteins, remove the heme cofactor, and shuttle heme into the cytoplasm for use as a nutrient iron source. Deletion of Isd system components decreases staphylococcal virulence, underscoring the importance of heme-iron acquisition during infection. In addition to heme, S. aureus can utilize transferrin-iron through the secretion of siderophores. Several staphylococcal siderophores have been described, some of which have defined roles during the pathogenesis of staphylococcal infections. A greater understanding of staphylococcal iron acquisition may lead to the development of novel therapeutic strategies that target nutrient uptake and decrease the threat of this increasingly drug-resistant bacterial pathogen.

Further reading: Iron Uptake and Homeostasis in Microorganisms

Labels: Heme, Heme uptake, Iron acquisition mechanisms, Iron transporters, Iron uptake in Staphylococci, Iron uptake systems, Iron-homeostasis, Iron-uptake, Siderophore, Siderophores, Staphylococci

Bacillus subtilis is a metabolically versatile soil microbe and Gram-positive model organism that displays a sophisticated adaptive response to conditions of iron limitation. The endogenous siderophore of B. subtilis is bacillibactin, a trimeric catecholate siderophore similar in structure to enterobactin. In addition to bacillibactin, B. subtilis can obtain iron from several xenosiderophores, ferric citrate, heme, and through a newly discovered elemental iron permease.

The regulation of iron homeostasis in B. subtilis is complex and involves a ferric uptake regulator (Fur) protein as master regulator and at least two subsidiary regulatory systems. The most significant of these is an iron-sparing/prioritization response controlled by the small RNA FsrA and three auxiliary proteins (FbpABC). In addition, the bacillibactin uptake system is transcriptionally activated by an AraC family activator, Btr that directly senses bacillibactin. Iron uptake and homeostasis systems in B. anthracis and related organisms are largely similar to those in B. subtilis with some additional components. These include a second siderophore synthesis operon for petrobactin, which is important for virulence, and a more elaborate (or at least better understood) heme uptake system.

Further reading: Iron Uptake and Homeostasis in Microorganisms

Labels: bacillus, Iron acquisition mechanisms, Iron deficiency, Iron transporters, Iron uptake in Bacillus, Iron uptake systems, Iron-homeostasis, Iron-uptake, Siderophore, Siderophores

Cyanobacteria are dependent on but can also be compromised by metals such as iron. On the one hand the demand for iron for photosystem functionality represents a challenge for the iron uptake machinery in iron limiting environments. On the other hand intoxication by iron causes a severe problem for growth and reproduction. To overcome this dilemma cyanobacteria have developed a regulatory network controlling iron uptake. They produce siderophores, which are distinct from that of other bacteria. Furthermore, the iron metabolism is linked to the nitrogen metabolism as documented for example in Anabaena sp. PCC 7120.

Further reading: Iron Uptake and Homeostasis in Microorganisms

Labels: Anabaena, cyanobacteria, Iron acquisition mechanisms, Iron deficiency, Iron transporters, Iron uptake in Cyanobacteria, Iron uptake systems, Iron-homeostasis, Iron-uptake, Siderophore, Siderophores

Upon colonization of the mammalian respiratory epithelium by mucosal pathogens of the genus Bordetella, the host-pathogen interaction causes inflammatory changes, immune activation, and host cell injury. In this dynamic environment, Bordetella cells scavenge the nutritional iron necessary for growth. The three classical Bordetella species produce the siderophore alcaligin. In addition, they can utilize xenosiderophores that could be produced by commensals or other microbes that transiently inhabit the nasopharynx.

As infection progresses, extravasation of immune cells, erythrocytes and serum to the mucosal surface can occur, exacerbated by the damaging action of Bordetella toxins, thus providing iron sources such as transferrin and heme compounds to the microbe. The three characterized Bordetella iron systems for utilization of alcaligin, enterobactin and heme are each inducible by the cognate iron source. The ability to sense and respond to the presence of available iron sources allows these pathogens to adapt to temporal changes in iron source availability, and this ability is important for successful in vivo growth.

Further reading: Iron Uptake and Homeostasis in Microorganisms

Labels: Bordetella, Iron acquisition mechanisms, Iron deficiency, Iron extraction, Iron transporters, pertussis, Siderophore, Siderophores