Version 2 2020-03-24, 12:37Version 2 2020-03-24, 12:37
Version 1 2018-12-17, 22:06Version 1 2018-12-17, 22:06
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posted on 2020-03-24, 12:37authored bySvenja Siemer, Dana Westmeier, Cecilia Vallet, Sven Becker, Jens Voskuhl, Guo-Bin Ding, Eckhard Thines, Roland H. Stauber, Shirley K. Knauer
Fungal infections are a growing global health and agricultural
threat, and current chemical antifungals may induce various side-effects.
Thus, nanoparticles are investigated as potential novel antifungals.
We report that nanoparticles’ antifungal activity strongly
depends on their binding to fungal spores, focusing on the clinically
important fungal pathogen Aspergillus fumigatus as well as common plant pathogens, such as Botrytis
cinerea. We show that nanoparticle–spore complex
formation was enhanced by the small nanoparticle size rather than
the material, shape or charge, and could not be prevented by steric
surface modifications. Fungal resistance to metal-based nanoparticles,
such as ZnO-, Ag-, or CuO-nanoparticles as well as dissolution-resistant
quantum dots, was mediated by biomolecule coronas acquired in pathophysiological
and ecological environments, including the lung surfactant, plasma
or complex organic matters. Mechanistically, dose-dependent corona-mediated
resistance occurred via reducing physical adsorption of nanoparticles
to fungal spores. The inhibitory effect of biomolecules on the antifungal
activity of Ag-nanoparticles was further verified in vivo, using the
invertebrate Galleria mellonella as
an A. fumigatus infection model. Our
results explain why current nanoantifungals often show low activity
in realistic application environments, and will guide nanomaterial
designs that maximize functionality and safe translatability as potent
antifungals for human health, biotechnology, and agriculture.