A. fumigatus A. flavus, A. niger, A. terreus causes a broad spectrum of disease in humans such as invasive and non-invasive aspergillosis ( Morgan et al., 2005 ). Invasive aspergillosis remains a major cause of morbidity and mortality in immunosuppressed patient (Patterson et al., 2000 ). Aspergillus is responsible for a range of diseases such as allergic diseases (asthma, allergic sinusitis, and alveolitis), invasive aspergillosis, allergic bronchopulmonary aspergillosis (Kumar et al., 2011 ). Exoproteins are the primary fungal components involved in host¿fungal interactions (Lowe RG, et al., 2012 ). The exoproteins of Aspergillus such as gliotoxin, hydrolases (alkaline protease, amylase, lipase, catalase) are important factor of virulence (Selvam et. al., 2014). Small-molecule epigenetic modifiers are effective tools for rationally controlling the native expression of fungal biosynthetic pathways. The aim of this work will be to determine the modulation of the extracellular proteins production of Aspergillus spp. using selective epigenetic inhibitor molecules, identify the mechanisms involved, with the aim of being able to use active molecules to reduce Aspergillus virulence.
Aspergillosis is a mycotic disease usually caused by A. fumigatus A. flavus, A. niger, A. terreus., a saprophytic and ubiquitous airborne funguses (M.L.Chabi et all, 2015). The incidence of Aspergillus infection has increased in the last years due to the use of immunosuppressive and immunomodulatory drugs and is still causing significant morbidity and mortality worldwide, especially in immunosuppressed patients (Marr KA et all, 2002). Fungal virulence factors, many of which are extracellular, facilitate hyphal invasion of the tissue (Girard V, et all, 2013). Their pathogenicity relies on this arsenal of exoproteins and their orchestrated release upon changing environmental conditions (J.Armengaud, et all, 2017). The study of secretory proteins seems to be of value in the discovery of circulating biomarkers that may play an important role in prompt diagnosis as well as targeted therapeutic developments. One the one hand, the pathogenic mechanisms of Aspergillus infection of human remain poorly understood (Hedayati MT, et. al., 2009). One the another hand, therapeutic options for aspergillosis are limited, particularly so for oral formulations, with azole drugs forming the backbone of therapy (Walsh TJ, et all, 2008). Many patients that develop resistant infections fail treatment, so resistance is an important factor in the outcome of these cases (Howard SJ, et all, 2009). Epigenetic modifiers are effective tools for rationally controlling the native expression of fungal biosynthetic pathways, reduce Aspergillus virulence. Using selective acetylation and methylation agents can help to overcome drug resistant. New therapies such as epigenetic modulation agent, appear promising and additional agents with new targets of action are urgently needed.