Author:
Marcos Caroline Maria,Tamer Gabrielle,de Oliveira Haroldo Cesar,Assato Patricia Akemi,Scorzoni Liliana,Santos Claudia Tavares,de Lacorte Singulani Junya,de Fátima da Silva Julhiany,de Almeida Rodrigo,de Paula e Silva Ana Carolina Alves,da Silva Rosangela Aparecida Moraes,de Andrade Cleverton Roberto,Tamayo Diana Patricia,Lopez Angela Maria,Barbosa Natália Moreira,Zanelli Cleslei Fernando,Hernandez- Ruiz Orville,McEwen Juan G.,Mendes-Giannini Maria José Soares,Fusco-Almeida Ana Marisa
Abstract
AbstractThe genusParacoccidioidesconsist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by whichParacoccidioidesspp. causes the disease remain poorly understood.Paracoccidioidesspp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) inParacoccidioides brasiliensis(PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence inGalleria mellonellaand murine infection models, emphasizing the importance of PbTufM in the full virulence ofP. brasiliensisand its potential as a target for antifungal agents against paracoccidioidomycosis.
Publisher
Springer Science and Business Media LLC
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