Santos, Ana LBeckham, Jacob LLiu, DongdongLi, Gangvan Venrooy, AlexisOliver, AntonioTegos, George PTour, James M2024-10-092024-10-092023-04Santos AL, Beckham JL, Liu D, Li G, van Venrooy A, Oliver A, et al. Visible-Light-Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload. Adv Sci (Weinheim, Baden-Wurttemberg, Ger. 2023 Jan;e2205781.https://hdl.handle.net/20.500.13003/18916https://hdl.handle.net/20.500.12105/23803Invasive 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.enghttp://creativecommons.org/licenses/by/4.0/Antifungal AgentsFungiCalciumAnimalsSwineresearch articleAtribución 4.0 Internacional367155881010e220578110.1002/advs.2022057812198-3844Advanced science (Weinheim, Baden-Wurttemberg, Germany)open accessAnimalesPorcinosHongosCalcioAntifúngicos2-s2.0-85147293639921666100001