The increased mortality of invasive fungal infections and the inefficient and inadequate antifungals necessitates the development of new agents with novel mechanisms and targets. The fungal cell wall has been the prime target as it contains polysaccharides absent in humans, however, its molecular structure remains elusive. Solid-state NMR (SSNMR) spectroscopy in combination with dynamic nuclear polarization and glycosyl linkage analysis, revealed that chitin and α-1,3- glucan build a hydrophobic moiety that is bordered by a hydrated matrix of diversely linked β-glucans and capped by a dynamic layer of glycoproteins and α-1,3-glucan. This study provided a high-resolution model of fungal cell walls, which is necessary for assessing drug response to promote the development of well-targeted antifungals. Among the antifungals drugs that have so far been used against aspergillosis, caspofungin, belonging to the echinocandin family, successfully reduced the amount of β-1,3-glucan as has been found via SSNMR studies. This β-1,3-glucan is the most abundant and hydrated polysaccharide in Aspergillus fumigatus. The genetic mutations resulting in cell wall polysaccharide removal have resulted in different compositions of the remaining components as well as altered nanoscale dynamics. The scarcity of the outer cell wall polysaccharide galactomannan brought about an increase in chitin content, highlighting its role in the rigid portion whereas another outer cell wall polysaccharide galactosaminogalactan hardly play any role there as its removal did not affect that region. The changes in the hydration and the mobility of the polysaccharides identified by SSNMR studies helped deduce the architectural changes in Aspergillus fumigatus at nanoscale resolution.

The role of polysaccharides in Aspergillus fumigatus

ACS Spring Meeting 2021

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