Gaining ultrastructural insight into the chitin layer of the model organism Saccharomyces cerevisiae to mediate drug development research

In the last decades, systemic fungal infections became a rising problem of global public health [ 1 ], mainly because resistances of fungal pathogens against common antimycotics like azoles, echinocandins and polyenes have increased strongly [ 2 ]. Hence, the development of innovative antimycotics is of specific importance today. Since the unique triple-layered fungal cell wall is required for cell stability and cell division, it is considered a promising target to develop selective and efficient antimycotic drugs [ 3 ]. In antiinfective drug research, lead structures frequently lack effectiveness against whole cells [ 4 ] because of defense mechanisms exerted by the targeted pathogens (e.g. activity of efflux transporters or limited cell wall permeability). To identify chitin inhibitors with activity against whole cells, we developed fluorescence and atomic force microscopy (AFM) bioimaging assays allowing to evaluate effects of chitin-synthase inhibitors on the composition and architecture of the cell wall chitin layer on a single cell basis. With the ability to isolate and nanoscopically characterize the chitin layer of the model organism Saccharomyces cerevisiae var. boulardii by AFM, effects of antifungal drug candidates can be studied in unprecedented detail ([ Fig. 1 ]). Fig. 1 Isolated chitin fibrils of Saccharomyces Cerevisiae captured with Atomic Force Microscopy In conclusion, our assays allow closer insight into chitin synthesis inhibition and will prospectively enable the direct assessment of antifungal effects against whole cells. Altogether, these assays could simplify the development of cell wall inhibiting antimycotics. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany