Résumé:
« Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Due to its high mortality rate and low susceptibility to antifungals, there is an urgent need to develop new therapeutic strategies against it. Since microbial lectins are often involved in host recognition and adhesion, they constitute valuable drug targets and have aimed at for the development of antiadhesive therapy against other deadly pathogens. However, in the case of S. apiospermum, the development of such therapies is hindered because its lectins are unknown. Therefore, the main aim of this work was the identification and characterization of S. apiospermum lectins. This has been addressed by two different approaches: the first strategy comprises the in-silico prediction of putative lectins codified on its genome by data mining, while the second strategy lies in the identification of native lectins from fungal protein extracts. These approaches have led to the identification of several proteins with carbohydrate-binding activity from this human pathogen. The preliminary analysis of those proteins reveals that some of them are potential pharmacological targets and others could find application as biotechnological tools.
A second objective of this thesis was the development of a new tool that allows the identification and purification of unknown lectins directly from crude protein extracts. This device also enables the study of lectin carbohydrate interactions without the need for fluorescent labeling. Therefore, it could greatly contribute to the future study of lectinome from other organisms.
Overall, this work represents a broad strategy to approach the study of S. apiospermum lectinome and our findings contribute to the understanding of the glycosylated surfaces recognition by this pathogen. We hope that the information gathered here will encourage the study of the proteins discovered to gain fundamental knowledge and for potential biomedical or biotechnological applications. »
