Secreted aspartyl proteinase (PbSap) contributes to the virulence of Paracoccidioides brasiliensis infection.

PLoS Negl Trop Dis 2018 09 27;12(9):e0006806. Epub 2018 Sep 27.

Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Paracoccidioidomycosis (PCM) is the most prevalent deep mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. Virulence factors are important fungal characteristics that support the development of disease. Aspartyl proteases (Saps) are virulence factors in many human fungal pathogens that play an important role in the host invasion process. We report here that immunization with recombinant Sap from Paracoccidioides brasiliensis (rPbSap) imparted a protective effect in an experimental PCM model. The rPbSap-immunized mice had decreased fungal loads, and their lung parenchyma were notably preserved. An aspartyl protease inhibitor (pepstatin A) significantly decreased pulmonary injury and reduced fungal loads in the lung. Additionally, we observed that pepstatin A enhanced the fungicidal and phagocytic profile of macrophages against P. brasiliensis. Furthermore, PbSAP expression was highly altered by environmental conditions, including thermal stress, dimorphism switching and low pH. Hence, our data suggest that PbSap is an important virulence regulator in P. brasiliensis.

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http://dx.doi.org/10.1371/journal.pntd.0006806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177206PMC

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September 2018
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References

(Supplied by CrossRef)
Principles and Practice of Infectious Diseases
A Restrepo et al.
2015
Molecular cloning of the cDNA and gene for an elastinolytic aspartic proteinase from Aspergillus fumigatus and evidence of its secretion by the fungus during invasion of the host lung
JD Lee et al.
Infect Immun 1995

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