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Key Fungal Secreted Proteases in Coccidioidomycosis

Summary

Researchers studied how a dangerous fungus called Coccidioides causes disease by examining special proteins called proteases that the fungus secretes. They found that blocking these proteases prevented the fungus from forming the spherule structures that allow it to spread inside infected people. This discovery could lead to new treatments for coccidioidomycosis, a serious infection that affects people in the Southwest United States.

Background

Coccidioides is a dimorphic fungus endemic to the Southwest United States that causes significant morbidity and mortality. The fungus’s virulence stems from its unique spherule form in host tissue, where spores develop into spherules that fill with endospores before rupturing. Coccidioides genomes encode expanded families of proteases (subtilases and deuterolysins) that are hypothesized to be involved in this spherulation process.

Objective

To characterize the role of fungal secreted proteases in spherule biology and spherulation of Coccidioides. The study aimed to identify protease families involved in the spherule development process as potential treatment targets.

Results

Subtilase inhibition prevented spherule formation, demonstrating a role for subtilases in spherulation. Subtilase and deuterolysin expression showed four distinct patterns during spherule development, with Sub1 being a major contributor to secreted protease activity and showing preference for hydrophobic substrates. Sub1 was among the top 10 most abundant transcripts in spherules during endospore release.

Conclusion

The study demonstrates the importance of expanded protease families in Coccidioides virulence, linking protease activity directly to spherulation and identifying these proteases as promising therapeutic targets for treatment development.
  • Published in:Open Forum Infectious Diseases,
  • Study Type:Basic Research,
  • Source: 10.1093/ofid/ofae631.1207, PMC11776737
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