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Morphogenesis and pathogenicity of Histoplasma capsulatum
Abstract:
The sulfhydryl blocking agent p-chloromercuriphenylsulfonic acid (PCMS) irreversibly inhibited the mycelium-to-yeast transitions of two virulent strains of Histoplasma capsulatum, G184A and G222B, when the temperature of incubation was raised to 37 degrees C, and the block persisted even after the cultures were washed free of PCMS. Instead of transforming to yeast cells, PCMS-treated mycelia continued to grow as mycelia at the elevated temperatures. A less virulent strain (Downs) was more temperature sensitive, but it showed a similar irreversible effect at 34 degrees C. Therefore, the mycelium-to-yeast transition of H. capsulatum is not required for the adaptation of mycelia to elevated temperatures but probably results from the temperature-dependent activation of yeast-specific genes. The transition to yeast is inferred to be obligate for pathogenicity in mice because PCMS-treated mycelia failed to cause infection, and no fungi were seen in tissues after PCMS-treated mycelia were injected into mice.
Insights
The sulfhydryl blocking agent p-chloromercuriphenylsulfonic acid (PCMS) prevents Histoplasma capsulatum from transforming into yeast at higher temperatures. This transition is essential for the fungus to cause infection in mice.
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.