Morphogenesis and pathogenicity of Histoplasma capsulatum

Area of Science:

• Medical Mycology
• Fungal Pathogenesis
• Molecular Biology

Background:

• Histoplasma capsulatum exists as mycelia at ambient temperatures and yeast at body temperatures.
• The mycelium-to-yeast transition is crucial for H. capsulatum pathogenesis.
• Environmental cues, such as temperature, regulate this dimorphic transition.

Purpose of the Study:

• To investigate the role of the mycelium-to-yeast transition in H. capsulatum adaptation to elevated temperatures.
• To determine if the transition is essential for H. capsulatum pathogenicity.

Main Methods:

• Utilized p-chloromercuriphenylsulfonic acid (PCMS), a sulfhydryl blocking agent, to inhibit the dimorphic transition.
• Incubated virulent and less virulent H. capsulatum strains at elevated temperatures (37°C and 34°C) with and without PCMS.
• Assessed fungal morphology and pathogenicity in a murine model after PCMS treatment.

Main Results:

• PCMS irreversibly blocked the mycelium-to-yeast transition in virulent H. capsulatum strains at 37°C and a less virulent strain at 34°C.
• PCMS-treated mycelia continued to grow as mycelia at elevated temperatures, indicating the transition is not required for temperature adaptation.
• PCMS-treated H. capsulatum failed to cause infection in mice, suggesting the yeast form is essential for pathogenicity.

Conclusions:

• The mycelium-to-yeast transition in H. capsulatum is not necessary for adaptation to higher temperatures but likely involves the activation of yeast-specific genes.
• The transition to the yeast form is an obligate step for H. capsulatum to establish infection in mammalian hosts.