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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
Iron uptake and virulence in Histoplasma capsulatum
Simon L Newman1, A George Smulian
1Department of Internal Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Abstract:
Histoplasma capsulatum (Hc) is the causative organism of a spectrum of disease affecting both the immunocompetent and the immunocompromised host. Hc is a dimporhic fungus that converts from conidia to the pathogenic yeast phase after entry into the mammalian host. Despite rapid ingestion by macrophages, it survives intracellularly within the macrophage. The intracellular survival strategy of Hc yeasts focuses on regulating the phagosomal compartment by modulating the intraphagosomal pH to 6.5. As an intracellular pathogen of MΦ, Hc obtains iron from Fe-transferrin, ferritin, or both, via the production of hydroxamate siderophores, and the production of ferric reductases. A better understanding of the mechanisms by which Hc yeasts acquire iron from the host may lead to novel therapeutics for histoplasmosis.
Insights
Histoplasma capsulatum (Hc) causes disease by surviving inside macrophages. Understanding how this fungus acquires iron is key to developing new treatments for histoplasmosis.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Host-Pathogen Interactions
Background:
- Histoplasma capsulatum (Hc) is a dimorphic fungus causing histoplasmosis in various hosts.
- Hc survives intracellularly within macrophages, modulating phagosomal pH to 6.5 for survival.
- Iron acquisition is crucial for Hc intracellular pathogenesis.
Purpose of the Study:
- To elucidate the iron acquisition mechanisms employed by intracellular Histoplasma capsulatum yeasts.
- To identify potential therapeutic targets for histoplasmosis based on Hc iron metabolism.
Main Methods:
- Analysis of Hc's interaction with host iron sources (Fe-transferrin, ferritin).
- Investigation of Hc's production of hydroxamate siderophores and ferric reductases.
- Study of the role of phagosomal pH regulation in Hc's intracellular survival.
Main Results:
- Hc utilizes hydroxamate siderophores and ferric reductases to obtain iron from host sources.
- Modulation of phagosomal pH to approximately 6.5 is critical for Hc intracellular survival.
- Iron acquisition is essential for the pathogenic yeast phase of Hc.
Conclusions:
- Hc employs specific iron scavenging mechanisms to thrive within macrophages.
- Targeting Hc iron acquisition pathways presents a promising strategy for novel histoplasmosis therapies.
