Abstract

Aspergillus fumigatus is the main etiological agent of invasive aspergillosis. This opportunistic fungus infection has high mortality rates and mainly affects neutropenic patients of Hematological Units, especially with acute leukemia and bone marrow transplantation recipients. The difficulty on establishing early diagnosis as well as the poor spectrum of antifungal drugs remains a setback to the successful treatment of this disease. Novel approaches to early detection of subclinical infections could improve prognosis. It was observed that germ tubes of A. fumigatus, independent of cell viability, cause injury to endothelial cells (ECs). Furthermore, hyphae but not conidia was able to activate ECs which express, in response, CD142, E-selectin and ICAM-1, potential markers of fungus angioinvasion. The proteomics technology is a powerful tool to search new diagnostic biomarkers and/or new drug targets of fungal infections. The aim of this work was to study differentially expressed proteins of A. fumigatus during the morphogenesis that occurs during the invasive infection by this pathogen. To reach this goal a 2D-DIGE approach was applied to study surface proteins obtained using a reducing agent treatment of A. fumigatus (AF293) intact cells of two morphotypes: (a) germ tubes (GT6h) and; (b) hyphae (H72h). The software DeCyder 7.0 was used to analyze these extracts and, 296 proteins were statistically validated for the 2D-DIGE maps. The GT6h cells presented 42.6% proteins overexpressed in relation to the hyphae while the H72h cells had 28% proteins overexpressed in relation to the germlings. Sixty-three of the differentially expressed were identified by MALDI-ToF/MS. Among the identified proteins at least two can be considered as good candidates as new drug targets. ਀ Support by CNPq, PPSUS-Faperj and CAPES.਀㰀⼀昀漀渀琀㸀㰀⼀瀀㸀㰀戀爀㸀㰀戀㸀䬀攀礀眀漀爀搀㨀 㰀⼀戀㸀☀渀戀猀瀀㬀䄀猀瀀攀爀最椀氀氀甀猀 昀甀洀椀最愀琀甀猀Ⰰ 搀爀甀最 琀愀爀最攀琀猀Ⰰ 瀀爀漀琀攀漀洀攀㰀⼀琀搀㸀㰀⼀琀爀㸀㰀⼀琀愀戀氀攀㸀㰀⼀琀爀㸀㰀⼀琀搀㸀㰀⼀琀愀戀氀攀㸀㰀⼀戀漀搀礀㸀㰀⼀栀琀洀氀㸀