Iron Uptake and Virulence
All living organisms need iron to survive. Iron is involved mainly in electron transfer reactions. Many parasites have a high iron requirement. In mammals, iron is closely regulated. Extracellular free iron is essentially unavailable and iron availability has a crucial role in the fight against pathogens. In plasma, circulating iron is bound to transferrin and in external secretions such as colostrum, iron is bound to lactoferrin. Therefore, microbial pathogens have developed specialized and effective mechanisms to acquire iron during infections (Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence. Trends in Microbiology 2008 16: 261-268).
Pathogens use two general strategies for iron acquisition from their hosts. The first is direct contact between the pathogen and the host iron source (usually an iron-containing protein). The second strategy uses secretion and subsequent uptake of small iron-binding molecules called siderophores, which are able to remove iron from host proteins because of their high affinity for the metal. These systems have been studied in many different pathogens.
Iron-acquisition strategies of fungi essentially consist of siderophore production, reductive iron-uptake and haem-uptake systems. Some fungi make siderophores, others do not, including the pathogenic Candida albicans. However, even species which cannot produce any siderophores can take up xenosiderophores – siderophores produced by other organisms (bacteria and fungi).
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Trypanosoma brucei is a protozoan parasite responsible for sleeping sickness in humans and a disease Nagana in domestic livestock in Africa. Trypanosomes obtain iron from host transferrin, and encode a number of different transferrin receptors which vary in their affinities for transferrins from different host species. Leishmania are parasites that require a sand fly vector and a mammalian host to complete their life cycle. As expected from the diversity of the environments Leishmania encounters during its life cycle, this parasite is able to use iron from several sources, such as transferrin, lactoferrin or haemin.
Because of the importance of iron to pathogens, siderophore-blocking drugs could turn out to be effective antimicrobial compunds against organisms which rely on this method of iron uptake, although none are in use yet. Another mystery of pathogen iron metabolism is iron storage. Once the cell takes up iron, it must be safely sequestered or it would participate in the generation of reactive oxygen species. In most organisms, this is ensured by iron-storage proteins, mainly ferritin. The majority of unicellular eukaryotes, such as yeast and parasitic protists, do not possess ferritin and the mechanism of intracellular iron storage in these organisms is not clear. In yeasts, the vacuole seems to have the function of an iron-storage compartment. It is important to complete our knowledge of the mechanisms of iron metabolism in pathogens because this might lead to the development of novel chemotherapeutic strategies. Without effective mechanisms for acquisition and utilization of iron, no parasite can survive.
Related:
- Utilization of iron by Campylobacter jejuni
- Bacillus anthracis gets iron from hemoglobin
- Magnetic Bacteria
Tags: Bacteria, Biology, Microbiology, Podcast, Science
My eyesight is failing me…B-(
I read that as “Iron Uptake and Flatulence”.
Ah, well.