PMID- 30260953
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20190114
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 12
IP  - 9
DP  - 2018 Sep
TI  - Secreted aspartyl proteinase (PbSap) contributes to the virulence of 
      Paracoccidioides brasiliensis infection.
PG  - e0006806
LID - 10.1371/journal.pntd.0006806 [doi]
LID - e0006806
AB  - 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.
FAU - Castilho, Daniele Goncalves
AU  - Castilho DG
AD  - Department of Microbiology, Immunology and Parasitology, Universidade Federal de 
      Sao Paulo, Sao Paulo, SP, Brazil.
FAU - Chaves, Alison Felipe Alencar
AU  - Chaves AFA
AD  - Department of Microbiology, Immunology and Parasitology, Universidade Federal de 
      Sao Paulo, Sao Paulo, SP, Brazil.
FAU - Navarro, Marina Valente
AU  - Navarro MV
AD  - Department of Microbiology, Immunology and Parasitology, Universidade Federal de 
      Sao Paulo, Sao Paulo, SP, Brazil.
FAU - Conceicao, Palloma Mendes
AU  - Conceicao PM
AD  - Department of Pharmaceutical Sciences, Instituto de Ciencias Ambientais, Quimicas 
      e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema, SP, Brazil.
FAU - Ferreira, Karen Spadari
AU  - Ferreira KS
AD  - Department of Pharmaceutical Sciences, Instituto de Ciencias Ambientais, Quimicas 
      e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema, SP, Brazil.
FAU - da Silva, Luiz Severino
AU  - da Silva LS
AD  - Department of Microbiology, Immunology and Parasitology, Universidade Federal de 
      Sao Paulo, Sao Paulo, SP, Brazil.
FAU - Xander, Patricia
AU  - Xander P
AD  - Department of Pharmaceutical Sciences, Instituto de Ciencias Ambientais, Quimicas 
      e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema, SP, Brazil.
FAU - Batista, Wagner Luiz
AU  - Batista WL
AUID- ORCID: 0000-0003-0280-6828
AD  - Department of Microbiology, Immunology and Parasitology, Universidade Federal de 
      Sao Paulo, Sao Paulo, SP, Brazil.
AD  - Department of Pharmaceutical Sciences, Instituto de Ciencias Ambientais, Quimicas 
      e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema, SP, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180927
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Virulence Factors)
RN  - EC 3.4.- (Aspartic Acid Proteases)
SB  - IM
MH  - Animals
MH  - Aspartic Acid Proteases/immunology/*metabolism
MH  - Colony Count, Microbial
MH  - Disease Models, Animal
MH  - Immunization
MH  - Lung/pathology
MH  - Macrophages/immunology
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Paracoccidioides/*enzymology/*pathogenicity
MH  - Paracoccidioidomycosis/immunology/microbiology/*pathology
MH  - Virulence
MH  - Virulence Factors/immunology/*metabolism
PMC - PMC6177206
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/09/28 06:00
MHDA- 2019/01/15 06:00
PMCR- 2018/09/27
CRDT- 2018/09/28 06:00
PHST- 2018/02/08 00:00 [received]
PHST- 2018/08/31 00:00 [accepted]
PHST- 2018/10/09 00:00 [revised]
PHST- 2018/09/28 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/09/28 06:00 [entrez]
PHST- 2018/09/27 00:00 [pmc-release]
AID - PNTD-D-18-00205 [pii]
AID - 10.1371/journal.pntd.0006806 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2018 Sep 27;12(9):e0006806. doi: 
      10.1371/journal.pntd.0006806. eCollection 2018 Sep.