Macrophage Interaction with Paracoccidioides brasiliensis Yeast Cells Modulates Fungal Metabolism and Generates a Response to Oxidative Stress.

Abstract

Macrophages are key players during Paracoccidioides brasiliensis infection. However, the relative contribution of the fungal response to counteracting macrophage activity remains poorly understood. In this work, we evaluated the P. brasiliensis proteomic response to macrophage internalization. A total of 308 differentially expressed proteins were detected in P. brasiliensis during infection. The positively regulated proteins included those involved in alternative carbon metabolism, such as enzymes involved in gluconeogenesis, beta-oxidation of fatty acids and amino acids catabolism. The down-regulated proteins during P. brasiliensis internalization in macrophages included those related to glycolysis and protein synthesis. Proteins involved in the oxidative stress response in P. brasiliensis yeast cells were also up-regulated during macrophage infection, including superoxide dismutases (SOD), thioredoxins (THX) and cytochrome c peroxidase (CCP). Antisense knockdown mutants evaluated the importance of CCP during macrophage infection. The results suggested that CCP is involved in a complex system of protection against oxidative stress and that gene silencing of this component of the antioxidant system diminished the survival of P. brasiliensis in macrophages and in a murine model of infection.

• Authors: Juliana Alves Parente-Rocha, Ana Flávia Alves Parente, Lilian Cristiane Baeza, Sheyla Maria Rondon Caixeta Bonfim, Orville Hernandez, Juan G McEwen, Alexandre Melo Bailão, Carlos Pelleschi Taborda, Clayton Luiz Borges, Célia Maria de Almeida Soares
• Journal: PloS one (PLoS One) Vol. 10 Issue 9 Pg. e0137619 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26360774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fungal Proteins
• Thioredoxins
• Cytochrome-c Peroxidase
• Superoxide Dismutase

Topics

• Animals
• Cell Line
• Cytochrome-c Peroxidase (genetics, metabolism)
• Down-Regulation
• Fungal Proteins (genetics, metabolism)
• Glycolysis
• Host-Pathogen Interactions
• Macrophages (microbiology)
• Mice
• Oxidative Stress
• Paracoccidioides (genetics, metabolism, pathogenicity)
• Superoxide Dismutase (genetics, metabolism)
• Thioredoxins (genetics, metabolism)