Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis

Author(s):Show less -

Marcos, Caroline Maria ^[1] ; Tamer, Gabrielle ^[1] ; de Oliveira, Haroldo Cesar ^{[2, 1]} ; Assato, Patricia Akemi ^[1] ; Scorzoni, Liliana ^{[1, 3]} ; Santos, Claudia Tavares ^[1] ; Singulani, Junya de Lacorte ^[1] ; da Silva, Julhiany de Fatima ^[1] ; de Almeida, Rodrigo ^[1] ; Alves de Paula e Silva, Ana Carolina ^[1] ; Moraes da Silva, Rosangela Aparecida ^[1] ; de Andrade, Cleverton Roberto ^[4] ; Tamayo, Diana Patricia ^[5] ; Lopez, Angela Maria ^[5] ; Barbosa, Natalia Moreira ^[6] ; Zanelli, Cleslei Fernando ^[6] ; Hernandez-Ruiz, Orville ^{[5, 7]} ; McEwen, Juan G. ^{[8, 5]} ; Soares Mendes-Giannini, Maria Jose ^[1] ; Fusco-Almeida, Ana Marisa ^[1]

Affiliation

^[1] UNESP Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Anal Clin, Lab Micol Clin, Campus Araraquara, Sao Paulo, SP - Brazil

^[2] Fundacao Oswaldo Cruz FIOCRUZ, Inst Carlos Chagas, Curitiba, Parana - Brazil

^[3] Sao Paulo State Univ UNESP, Inst Sci & Technol, Sao Jose Dos Campos, SP - Brazil

^[4] UNESP Univ Estadual Paulista, Fac Odontol, Dept Fisiol & Patol, Campus Araraquara, Sao Paulo, SP - Brazil

^[5] CIB, Unidad Biol Celular & Mol, Medellin - Colombia

^[6] UNESP Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, Lab Biol Mol & Celular Microrganismos, Campus Araraquara, Sao Paulo, SP - Brazil

^[7] Univ Antioquia, Escuela Microbiol, Grp Invest MICROBA, Medellin - Colombia

^[8] Univ Antioquia, Fac Med, Medellin - Colombia

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, NOV 20 2019.
• Web of Science Citations: 0

Abstract

The genus Paracoccidioides consist 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 which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. 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) in Paracoccidioides 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 in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis. (AU)

• FAPESP's process: 13/10917-9 - Alternative animal models: Virulence of different phylogenetic species of Paracoccidioides and effect of the 30kDa 43kDa protein and their antibodies
• Grantee: Liliana Scorzoni
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 16/17048-4 - Two-component signal transduction (TCST) system as a new target for the treatment of paracoccidioidomycosis
• Grantee: Caroline Maria Marcos
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/14023-8 - Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis
• Grantee: Haroldo Cesar de Oliveira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/03700-9 - Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments
• Grantee: Maria José Soares Mendes Giannini
• Support type: Regular Research Grants
• FAPESP's process: 14/10446-9 - Evaluation of new therapies and biomarkers in paracoccidioidomycosis: antifungal activity of alkyl gallates in alternative models and mice and identification of circulating microRNAs
• Grantee: Junya de Lacorte Singulani
• Support type: Scholarships in Brazil - Doctorate