Secreted aspartyl proteinase (PbSap) contributes to the virulence of Paracoccidioides brasiliensis infection.
Daniele Gonçalves CastilhoAlison Felipe Alencar ChavesMarina Valente NavarroPalloma Mendes ConceiçãoKaren Spadari FerreiraLuiz Severino da SilvaPatricia XanderWagner Luiz BatistaPublished in: PLoS neglected tropical diseases (2018)
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.
Keyphrases
- antimicrobial resistance
- pseudomonas aeruginosa
- escherichia coli
- staphylococcus aureus
- biofilm formation
- poor prognosis
- endothelial cells
- cystic fibrosis
- pulmonary hypertension
- candida albicans
- adipose tissue
- transcription factor
- gram negative
- high fat diet induced
- type diabetes
- multidrug resistant
- risk assessment
- cell migration
- long non coding rna
- climate change
- insulin resistance
- big data
- deep learning
- heat stress