PMID- 21728754
OWN - NLM
STAT- MEDLINE
DCOM- 20120404
LR  - 20131213
IS  - 1460-2709 (Electronic)
IS  - 1369-3786 (Linking)
VI  - 50
IP  - 1
DP  - 2012 Jan
TI  - Identification of a metallopeptidase with TOP-like activity in Paracoccidioides 
      brasiliensis, with increased expression in a virulent strain.
PG  - 81-90
LID - 10.3109/13693786.2011.590825 [doi]
AB  - Paracoccidioidomycosis (PCM), caused by the pathogenic fungus Paracoccidioides 
      brasiliensis, is a systemic mycosis with severe acute and chronic forms. The 
      pathology of PCM is not completely understood, and the role of proteases in the 
      infection is not clearly defined. In this report, we describe a metallopeptidase 
      activity in P. brasiliensis total and cytosolic protein extracts similar to that 
      of mammalian thimet oligopeptidase (TOP). The analogous enzyme was suggested by 
      analysis of P. brasiliensis genome databank and by hydrolytic activity of the 
      FRET peptide Abz-GFSPFRQ-EDDnp which was completely inhibited by o-phenanthrolin 
      and significantly inhibited by the TOP inhibitor, JA-2. This activity was also 
      partially inhibited by IgG purified from patients with PCM, but not from normal 
      individuals. As shown by high-performance liquid chromatography (HPLC), the 
      hydrolysis of bradykinin had the same pattern as that of mammalian TOP, and 
      anti-mammalian TOP antibodies significantly inhibited fungal cytosolic peptidase 
      activity. Moreover, anti-mammalian TOP antibodies recognized a component of 80 
      kDa on fungal cytosol. A P. brasiliensis virulent isolate showed higher gene 
      expression and TOP-like peptidase activity than a non-virulent strain. The 
      release of enzyme following fungal lysis would be consistent with host antibody 
      production and may have a role in the pathogenesis, inflammation and further 
      development of the mycosis.
FAU - Gravi, Ellen T
AU  - Gravi ET
AD  - Unidade de Oncologia Experimental (UNONEX), Departamento de Microbiologia, 
      Imunologia e Parasitologia, Universidade Federal de Sao Paulo-Escola Paulista de 
      Medicina (UNIFESP-EPM), Sao Paulo, SP, Brazil.
FAU - Paschoalin, Thaysa
AU  - Paschoalin T
FAU - Dias, Bianca R
AU  - Dias BR
FAU - Moreira, Dayson F
AU  - Moreira DF
FAU - Belizario, Jose E
AU  - Belizario JE
FAU - Oliveira, Vitor
AU  - Oliveira V
FAU - Carmona, Adriana K
AU  - Carmona AK
FAU - Juliano, Maria A
AU  - Juliano MA
FAU - Travassos, Luiz R
AU  - Travassos LR
FAU - Rodrigues, Elaine G
AU  - Rodrigues EG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110705
PL  - England
TA  - Med Mycol
JT  - Medical mycology
JID - 9815835
RN  - 0 (DNA, Fungal)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 3.4.- (Metalloproteases)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Animals
MH  - Bradykinin/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - DNA, Fungal/genetics
MH  - Enzyme Inhibitors/metabolism
MH  - *Gene Expression Profiling
MH  - Humans
MH  - Lung/microbiology
MH  - Male
MH  - Metalloproteases/antagonists & inhibitors/genetics/isolation & 
      purification/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Weight
MH  - Paracoccidioides/*enzymology/isolation & purification/*pathogenicity
MH  - Paracoccidioidomycosis/microbiology
MH  - Phylogeny
MH  - Sequence Homology, Amino Acid
MH  - Virulence
EDAT- 2011/07/07 06:00
MHDA- 2012/04/05 06:00
CRDT- 2011/07/07 06:00
PHST- 2011/07/07 06:00 [entrez]
PHST- 2011/07/07 06:00 [pubmed]
PHST- 2012/04/05 06:00 [medline]
AID - 10.3109/13693786.2011.590825 [doi]
PST - ppublish
SO  - Med Mycol. 2012 Jan;50(1):81-90. doi: 10.3109/13693786.2011.590825. Epub 2011 Jul 
      5.