Resumo

Paracoccidioides brasiliensis is the etiological agent of Paracoccidioidomycosis a systemic mycosis that affects around 10 million individuals in the endemic regions. The incidence of disease is high in Latin America and most of the cases are found in Brazil. The disease is characterized by a chronic granulomatous inflammation, and patients may present a broad spectrum of clinical manifestations. After host inhalation of mycelial propagules and fungal establishment in the lungs, it can be disseminated through the bloodstream. Hematogenous fungal infections represent a serious health problem, involving hospitalized patients with predisposing conditions that lead to a high mortality rate. Fungemia corresponds to the isolation of fungi in the bloodstream and occurs mostly in immunosuppressed patients. Yeasts have been increasingly present as etiological agents of fungemia, incuding Candida albicans and other species such as Candida non-albicans . Nevertheless, other fungi, such as Histoplasma capsulatum, may also be involved. In the present study P. brasiliensis was isolated from a fungemia case. To date that is the first case of fungemia caused by this fungus. In order to identify the molecular factors related to this specific phenotype a comparative proteomic analysis was performed. The samples were analyzed by nanoscale liquid chromatography coupled with tandem mass spectrometry (nanoUPLC-MS^E), where soluble proteins from fungemia strain were compared with Pb01-like proteins. nanoUPLC-MS^E assays revealed that 469 proteins were regulated in fungemia strain; which 76 were unique to Pb01-like, 122 were specific to fungemia, 36 were down-regulated and 226 were up-regulated. Proteins were identified and functionally classified according to the system Funcat2. Among the unique proteins from fungemia 32% of the total were related to cell metabolism, 14.5% related to protein synthesis, 10.7% related to energy and 10.5% related to protein fate. Regarding the protein up-regulated, 30% of the total were related to metabolism, 25% related to protein synthesis, 12% related to energy, 9.7% related to protein fate and 4.5% related to cell rescue, defense and virulence. The study of the proteomic profile of this isolate could elucidate the virulence mechanisms used by this fungus during fungemia and/or hematogenous dissemination.