Document Detail

A 32-kilodalton hydrolase plays an important role in Paracoccidioides brasiliensis adherence to host cells and influences pathogenicity.
MedLine Citation:
PMID:  20876288     Owner:  NLM     Status:  MEDLINE    
One of the most crucial events during infection with the dimorphic fungus Paracoccidioides brasiliensis is adhesion to pulmonary epithelial cells, a pivotal step in the establishment of disease. In this study, we have evaluated the relevance of a 32-kDa protein, a putative adhesion member of the haloacid dehalogenase (HAD) superfamily of hydrolases, in the virulence of this fungus. Protein sequence analyses have supported the inclusion of PbHad32p as a hydrolase and have revealed a conserved protein only among fungal dimorphic and filamentous pathogens that are closely phylogenetically related. To evaluate its role during the host-pathogen interaction, we have generated mitotically stable P. brasiliensis HAD32 (PbHAD32) antisense RNA (aRNA) strains with consistently reduced gene expression. Knockdown of PbHAD32 did not alter cell vitality or viability but induced morphological alterations in yeast cells. Moreover, yeast cells with reduced PbHAD32 expression were significantly affected in their capacity to adhere to human epithelial cells and presented decreased virulence in a mouse model of infection. These data support the hypothesis that PbHad32p binds to extracellular matrix (ECM) proteins and modulates the initial immune response for evasion of host defenses. Our findings point to PbHAD32 as a novel virulence factor active during the initial interaction with host cells in P. brasiliensis.
Orville Hernández; Agostinho J Almeida; Angel Gonzalez; Ana Maria Garcia; Diana Tamayo; Luz Elena Cano; Angela Restrepo; Juan G McEwen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-27
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-16     Completed Date:  2010-12-15     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5280-6     Citation Subset:  IM    
Instituto de Biología, Universidad de Antioquia, Medellín, Colombia.
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MeSH Terms
Cell Adhesion
Cell Line
Chemokines, CXC
Cytokines / biosynthesis,  physiology
Gene Expression Profiling
Gene Knockdown Techniques
Host-Pathogen Interactions / physiology
Hydrolases / metabolism
Mice, Inbred BALB C
Paracoccidioides / metabolism,  pathogenicity*,  physiology
Paracoccidioidomycosis / microbiology*
Respiratory Mucosa / microbiology
Reg. No./Substance:
0/Chemokines, CXC; 0/Cxcl15 protein, mouse; 0/Cytokines; EC 3.-/Hydrolases; EC dehalogenase

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