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Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload

Authors :
Ana L. Santos
Jacob L. Beckham
Dongdong Liu
Gang Li
Alexis vanVenrooy
Antonio Oliver
George P. Tegos
James M. Tour
Source :
Advanced Science, Vol 10, Iss 10, Pp n/a-n/a (2023)
Publication Year :
2023
Publisher :
Wiley, 2023.

Abstract

Abstract Invasive fungal infections are a growing public health threat. As fungi become increasingly resistant to existing drugs, new antifungals are urgently needed. Here, it is reported that 405‐nm‐visible‐light‐activated synthetic molecular machines (MMs) eliminate planktonic and biofilm fungal populations more effectively than conventional antifungals without resistance development. Mechanism‐of‐action studies show that MMs bind to fungal mitochondrial phospholipids. Upon visible light activation, rapid unidirectional drilling of MMs at ≈3 million cycles per second (MHz) results in mitochondrial dysfunction, calcium overload, and ultimately necrosis. Besides their direct antifungal effect, MMs synergize with conventional antifungals by impairing the activity of energy‐dependent efflux pumps. Finally, MMs potentiate standard antifungals both in vivo and in an ex vivo porcine model of onychomycosis, reducing the fungal burden associated with infection.

Details

Language :
English
ISSN :
21983844
Volume :
10
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Advanced Science
Publication Type :
Academic Journal
Accession number :
edsdoj.1780bd3f43414cad8ce153aaed5e4040
Document Type :
article
Full Text :
https://doi.org/10.1002/advs.202205781