Study of the filamentation of ISN1 from C. glabrata in the presence of its substrate IMP.

Candidemia, a bloodstream infection caused by Candida yeasts, represents a serious public health concern due to rising antifungal resistance. Candida glabrata, in particular, is known for its high resistance to conventional antifungal drugs, making the discovery of new therapeutic strategies an urgent priority.

To achieve this, the protein Isn1, a pivotal enzyme hydrolyzing both IMP (purine pathway) and possibly NMN (NAD pathway) is studied by X-ray crystallography, cryo-EM, and enzymology to uncover how ISN1 functions at the molecular level and to assess its potential as a novel antifungal target. Some preliminary data collected on the Glacios at IBS on the filamentous form of Isn1 gave a 3.17 A resolution. A data collection on a 300 kV microscope is now requested to reach a higher resolution that will allow a more complete description of the ligand biding as well as filament formation.