Utilization and cell-surface binding of hemin by Histoplasma capsulatum

Area of Science:

• Mycology
• Medical Mycology
• Infectious Diseases

Background:

• Histoplasma capsulatum causes respiratory illness in immunocompromised individuals.
• During infection, H. capsulatum resides in macrophages, requiring iron acquisition.
• Iron sources within macrophages include transferrin and intracellular heme.

Purpose of the Study:

• To investigate the ability of Histoplasma capsulatum to utilize hemin and heme-containing compounds as iron sources.
• To determine the mechanism of iron acquisition from heme by H. capsulatum.

Main Methods:

• Iron-starvation of H. capsulatum using deferoxamine mesylate.
• Culturing the fungus in iron-limited, chemically defined medium.
• Measuring hemin binding to yeast cell surfaces under different nutritional conditions.
• Assessing the effect of proteinase K and protoporphyrin IX on hemin binding.

Main Results:

• Hemin addition restored growth of iron-starved H. capsulatum.
• H. capsulatum could use hemoglobin as a sole iron source.
• Iron-limited cells exhibited higher hemin binding than cells grown in replete medium.
• Proteinase K treatment abolished hemin binding, indicating a protein receptor.
• Pre-incubation with hemin saturated the binding sites, while protoporphyrin IX had minimal effect.

Conclusions:

• Histoplasma capsulatum effectively utilizes hemin as a sole iron source.
• A cell-surface receptor mediates hemin uptake in H. capsulatum.
• This mechanism is crucial for iron acquisition during macrophage infection.