| Title: |
Hsp90/co-chaperone interaction : a new target for the treatment of invasive candidiasis ; L'interaction Hsp90/co-chaperonnes : nouvelle cible pour le traitement des candidoses invasives |
| Authors: |
Rouges, Célia |
| Contributors: |
Cibles et Médicaments des Infections et de l'Immunité - UR 1155 (IICiMed); Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Nantes Université; Patrice Le Pape; Pascal Marchand |
| Source: |
https://theses.hal.science/tel-04368941 ; Médecine humaine et pathologie. Nantes Université, 2023. Français. ⟨NNT : 2023NANU1011⟩. |
| Publisher Information: |
CCSD |
| Publication Year: |
2023 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
Sba1 protein; Hsp90 heat-shock protein; Cdc37 protein; Candida; Sba1; Hsp90; Cdc37; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Description: |
During the past decade systemic candidiasis incidence has increased placing the yeast Candida albicans at the fourth rank of pathogenic agent responsible for hospital- acquired infections. Emergence of antifungal resistance, host toxicity, drug interactions and paucity of target limit the current treatment strategies. To overcome these limitations as well as to improve our therapeutic armamentarium, original targets need to be identified to develop new antifungal alternatives. Hsp90, a chaperone well-studied in oncology, has been identified as an original target in medical mycology. Indeed, Hsp90 plays a key role in virulence and drug resistance to mains classes of antifungals. To our knowledge, the vast majority of inhibitors developed target the N-terminal domain of the protein. Our work focused on binding sites with a lower degree of interspecies homology. We hypothesised that the e-terminal domain of Hsp90 and its co- chaperones would be more selective targets because their protein sequences were less conserved. Thus, we described the anti-Candida activity of celastrol, a natural compound interacting with the co-chaperone Cdc37. Furthermore, at the end of this collaborative and multidisciplinary project, the modelling of the interaction of Hsp90 with Sba1 allowed the selection by high- throughput screening of other "hit" compounds that could serve as a basis for optimization towards "lead" compounds. ; L'incidence des candidoses invasives ne cesse d'augmenter ces dix dernières années plaçant la levure Candida albicans au quatrième rang des pathogènes responsables d'infections nosocomiales. L'émergence de résistances, les interactions médicamenteuses, la toxicité et la faible diversité de cibles, limitent les stratégies thérapeutiques. li apparaît donc nécessaire d'identifier de nouvelles cibles afin de développer des outils thérapeutiques innovants en mycologie médicale. La Heat-Shock-Protein 90kDa (Hsp90}, protéine chaperonne étudiée en cancérologie car impliquée dans la survie cellulaire, a également été ... |
| Document Type: |
doctoral or postdoctoral thesis |
| Language: |
French |
| Relation: |
NNT: 2023NANU1011 |
| Availability: |
https://theses.hal.science/tel-04368941; https://theses.hal.science/tel-04368941v1/document; https://theses.hal.science/tel-04368941v1/file/ROUGES.pdf |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.221E5BD1 |
| Database: |
BASE |