Study of Aspergillus fumigatus pathogenicity and identification of putative virulence genes

Résumé

Aspergillus fumigatus is considered to be the most prevalent airborne pathogenic fungus. lts infection begins with conidial germination in lungs where different types of aspergillosis can be developed. In profoundly immunocompromised individuals this pathogen can even disseminate via the bloodstream, resulting in a disseminated disease in which other organs might be infected. With the airo of improving our understanding of the pathogenicity mechanisms, a new expression microarray covering the entire genome of A. fumigatus was designed to analyze its transcriptome at the first steps of germination and along a disseminated infection. According to transcriptomic results, essential elements such as nitrogen, iron and zinc seemed to be available enough during the infection, raising doubts about the potential of metal uptake systems as therapeutic or diagnostic methods. However, genes involved in carbohydrate and secondary metabolism, and even those encoding unclassified and hypothetical proteins, stood out as indispensable pathways for extending the infection. This study also allowed the identification of genes whose expressions were enhanced along the infectious process and the implication in virulence of two of them was studied. The deletion of the abrl/ brownl gene developed an isolate with an increase in cell damage, suggesting that this knockout might produce and secrete a toxic intermediate. On the contrary, when a transcription factor was deleted a decrease in cell damage was observed, highlighting its implication in A. fumigatus pathogenecity. Nevertheless, more studies need to be done to assess whether any of them show attenuation in virulence and to shed light on the biological functions they are involved, which could lead to identify potentially targets to develop diagnostic or treatment strategies.