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

Vibrio and Aeromonas species are ubiquitous bacteria in aquatic environments worldwide. Many of the species are important pathogens for humans and/or aquatic animals. Several iron acquisition strategies have been developed by vibrios and aeromonads in order to get this essential element for surviving in their host and in aquatic habitats. All species studied so far have the ability to synthesize siderophores to sequester iron from the cell environment and transport it through their respective cognate outer membrane receptors. It has been demonstrated that this capacity is a relevant virulence factor for human and animal pathogens. Furthermore, all species studied can utilize exogenous siderophores, made by other bacteria. Another iron acquisition system described in both genera involves the use of heme as a source of iron, by a mechanism very well conserved among all species, which involves a heme transporter that includes a specific TonB-dependent outer membrane receptor(s) and an ABC-type inner membrane transporter. Alternative systems based on ferrous or ferric iron transporters have been reported in V. cholerae. How the different iron acquisition systems work together to supply iron to the cell and how they are used in the different environments where vibrios and aeromonads can be found is still an open question.

Further reading: Iron Uptake and Homeostasis in Microorganisms

Labels: Aeromonas, Exogenous heme, Heme biosynthesis pathway, Heme degradation, Heme efflux, Heme uptake, Iron acquisition strategies, Iron deficiency, Iron extraction, Iron uptake in Vibrio, vibrio

Heme is ubiquitous, abundant and necessary for energy metabolism. Most bacteria have a heme biosynthesis pathway, but nevertheless, since heme is a major source of iron (an essential metal), microbes take up exogenous heme to retrieve iron. To grab heme, microbes extract it from host hemoproteins. This is achieved by two non-exclusive distinct pathways. One pathway involves proteins secreted by bacteria (hemophores) that scavenge heme from host hemoproteins. The second pathway involves microbial cell surface receptors that catch hemoproteins circulating in the vicinity of the cell surface. Both pathways lead to heme docking to cell surface receptors. In Gram-negative bacteria, docked heme is transported through the outer membrane by an energy-dependent process. In Gram-positive bacteria, docked heme is transferred to membrane-anchored heme binding lipoproteins. In all thus far described systems, heme is actively transported through the plasma membrane by an ATP hydrolysis-powered ABC transporter. Heme is either degraded into biliverdin, CO and iron by heme oxygenases, or iron is retrieved from heme, keeping the tetrapyrrol ring intact by recently identified enzymes. As excess heme is toxic, heme uptake, efflux and degradation are usually highly regulated. In most cases, intracytoplasmic heme or iron released during heme degradation are cofactors along with transcriptional regulators. In several cases, heme uptake and efflux are regulated by extracellular heme.

Further reading: Iron Uptake and Homeostasis in Microorganisms

Labels: Exogenous heme, Haeme, Heme, Heme biosynthesis pathway, Heme degradation, Heme efflux, Heme uptake