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Role of paracoccin on Paracoccidioides brasiliensis virulence and susceptibility to antifungal drugs in the Galleria mellonella larvae model.
de Souza Pitangui, Nayla; Fernandes, Fabrício Freitas; Aparecido da Silva, Thiago; Gonçales, Relber Aguiar; Roque-Barreira, Maria Cristina.
Afiliación
  • de Souza Pitangui N; Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Fernandes FF; Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
  • Aparecido da Silva T; Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Virulence ; 14(1): 2150455, 2023 12.
Article en En | MEDLINE | ID: mdl-36599817
Paracoccin (PCN), a Paracoccidioides brasiliensis glycoprotein, has been reported to play roles in fungal biology and paracoccidioidomycosis pathogenesis. Lectin and chitinase domains account for the PCN's dual roles as an immunomodulatory agent and virulence factor. Soluble PCN injected in P. brasiliensis infected mice, by interacting with TLRs' N-glycans, drives the host immune response toward a protective Th1 axis. Otherwise, mice infection with yeasts overexpressing PCN (ov-PCN) revealed that PCN acts as a fungal virulence factor, thanks to its chitinase activity on the cell wall, resulting in resistance to phagocytes' fungicidal activity and development of severe paracoccidioidomycosis. Because antifungal drug administration follows the disease diagnosis, we studied the PCN effect on yeast resistance or susceptibility to antifungal agents. Using a paracoccidioidomycosis model developed in Galleria mellonella larvae, we confirmed the observation, in the murine host, that ov-PCN yeasts display maximum virulence compared to wild-type (wt-PCN) or PCN-silenced (kd-PCN) yeasts. PCN overexpression accounted for the highest susceptibility of P. brasiliensis to antifungal and reduced relative mRNA expression of genes encoding proteins related to cell wall remodeling. The lowest virulence, detected in infection with kd-PCN yeasts, correlated with the lowest susceptibility to antifungals and impact on genes for cell wall remodeling. So, we defined that the grade of endogenous PCN production influences the P. brasiliensis virulence and susceptibility to antifungal drugs, as well as the expression of genes related to cell wall remodeling. We postulate that this variable gene expression is mechanistically associated with P. brasiliensis virulence changes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paracoccidioides / Paracoccidioidomicosis / Mariposas Nocturnas Tipo de estudio: Prognostic_studies Límite: Animals País/Región como asunto: America do sul / Brasil Idioma: En Revista: Virulence Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paracoccidioides / Paracoccidioidomicosis / Mariposas Nocturnas Tipo de estudio: Prognostic_studies Límite: Animals País/Región como asunto: America do sul / Brasil Idioma: En Revista: Virulence Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos