Paracoccidioides brasiliensis presents metabolic reprogramming and secretes a serine proteinase during murine infection

巴西副球孢子菌在小鼠感染期间表现出代谢重编程并分泌丝氨酸蛋白酶

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作者:Laurine Lacerda Pigosso, Lilian Cristiane Baeza, Mariana Vieira Tomazett, Mariana Batista Rodrigues Faleiro, Veridiana Maria Brianezi Dignani de Moura, Alexandre Melo Bailão, Clayton Luiz Borges, Juliana Alves Parente Rocha, Gabriel Rocha Fernandes, Gregory M Gauthier, Celia Maria de Almeida Soares

Abstract

Paracoccidoides brasiliensis and Paracoccidioides lutzii, the etiologic agents of paracoccidioidomycosis, cause disease in healthy and immunocompromised persons in Latin America. We developed a method for harvesting P. brasiliensis yeast cells from infected murine lung to facilitate in vivo transcriptional and proteomic profiling. P. brasiliensis harvested at 6 h post-infection were analyzed using RNAseq and LC-MSE. In vivo yeast cells had 594 differentially expressed transcripts and 350 differentially expressed proteins. Integration of transcriptional and proteomic data indicated that early in infection (6 h), P. brasiliensis yeast cells underwent a shift in metabolism from glycolysis to β-oxidation, upregulated detoxifying enzymes to defend against oxidative stress, and repressed cell wall biosynthesis. Bioinformatics and functional analyses also demonstrated that a serine proteinase was upregulated and secreted in vivo. To our knowledge this is the first study depicting transcriptional and proteomic data of P. brasiliensis yeast cells upon 6 h post-infection of mouse lung.

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