14.4E: Siderophores

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Learning Objectives

Compare and contrast the role of various siderophores in pathogenecity, including: yersiniabactin, enterobactin and ferrichromes

Siderophores are specific types of molecules utilized by microorganisms to obtain iron from the environment. Specifically, in regards to pathogenicity, organisms that exhibit the ability to produce siderophores release these iron-specific molecules and scavenge iron from their hosts organisms. The siderophores are then utilized by the pathogen to obtain iron. Therefore, siderophores are chelating agents that bind the iron ions. The ability of pathogens to obtain iron from the host is essential for survival because the iron is limited in the host environment, in particular, the host tissues and fluids. The iron is used to allow for formation of soluble ferric ion (Fe3+) complexes that are necessary for maintenance of homeostatic mechanisms within the pathogen.

The ability to form water soluble Fe3+ complexes is a key component to the active transport of the Fe-siderophore complex across the cellular membrane. In iron deficient environments, the siderophores are released and allow for the formation of water soluble-Fe3+ complexes to increase iron acquisition. The complexes then generally bind to the cellular membrane using cell specific receptors. They are transported across the membrane utilized for the necessary processes. However, there are differences in the mechanisms employed by various sideorophobes to obtain iron and the specific type of siderophore utilized varies.

Yersiniabactin

The pathogenic bacteria, Yersinia pestis, Yersinia pseduotuberculosis, and Yersinia enterocolitica have the ability to produce a siderophore called yersiniabactin. Pathogenic yersinia is responsible for numerous diseases including the bubonic plague. The ability of pathogenic Yersinia to establish and spread disease is based on its ability to obtain iron for fundamental cellular processes. In areas of low iron, the organism will release yersiniabactin to form Fe3+ complexes. The yersiniabactin-Fe3+ complex will then bind to the outer membrane of the bacteria based on specific receptor recognition. The complex is then translocated through the membrane via membrane-embedded proteins and iron is released from the yersiniabactin. The iron will then be utilized in numerous cellular processes.

Enterobactin

Pathogenic bacteria such as Escherichia coli and Salmonella typhimurium have the ability to produce a siderophore called enterobactin. This specific type of siderophore is the strongest identified siderophore, to date, with an extremely high binding affinity to Fe3+. Upon a decrease in iron, the bacterial cells release enterobactin which forms a complex with Fe3+. The complex is then transported intracellularly via an ATP-binding cassette transporter. Once the enterobactin-Fe3+ complex arrives intracellularly, it is necessary to remove the Fe3+ from the complex. Due to the high-binding affinity of enterobactin, the bacteria require a highly specific enzyme, ferrienterobactin esterase, to cleave the iron from the complex. The iron released from the complex will then be utilized in metabolic processes.

Ferrichrome

Another type of siderophore produced by pathogenic fungi includes a ferrichrome. Fungi that have been shown to produce ferrichromes include those in the genera Aspergillus, Ustilago, and Penicillum. The ferrichrome allows for formation of a ferrichrome-iron complex which can then interact with a protein receptor on the cell surface. The ferrichrome promotes iron transport within the organism to allow metabolic processes to occur.

The discovery and identification of siderophores have allowed for the development of treatments targeting these siderophore-iron complexes. By targeting these complexes, the pathogenic microorganisms can be targeted by inhibiting necessary cellular processes. The production and importance of these siderophores to pathogenic organisms is key to their survival.

Key Points

Siderophore – iron complexes are necessary for iron acquisition to various pathogenic organisms for metabolic processes.
The types of siderophores produced are species specific and exhibit different properties.
The siderophores are necessary to obtain iron by binding to cell surfaces and transporting the siderophore-iron complexes intracellularly.
Siderophores are produced in environments that have low iron concentration, such as host tissues and fluids. They are considered advantageous to pathogenic organisms.

Key Terms

siderophore: Any medium-sized molecule that has a high specificity for binding or chelating iron; they are employed by microorganisms to obtain iron from the environment
chelating agent: A compound that reacts with a metal ion to produce a chelate.