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

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dc.citation.articleNumber2205781en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitleAdvanced Scienceen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorSantos, Ana L.en_US
dc.contributor.authorBeckham, Jacob L.en_US
dc.contributor.authorLiu, Dongdongen_US
dc.contributor.authorLi, Gangen_US
dc.contributor.authorvan Venrooy, Alexisen_US
dc.contributor.authorOliver, Antonioen_US
dc.contributor.authorTegos, George P.en_US
dc.contributor.authorTour, James M.en_US
dc.contributor.orgSmalley-Curl Instituteen_US
dc.contributor.orgNanoCarbon Centeren_US
dc.contributor.orgWelch Institute for Advanced Materialsen_US
dc.date.accessioned2023-04-25T14:47:44Zen_US
dc.date.available2023-04-25T14:47:44Zen_US
dc.date.issued2023en_US
dc.description.abstractInvasive 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.en_US
dc.identifier.citationSantos, Ana L., Beckham, Jacob L., Liu, Dongdong, et al.. "Visible-Light-Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload." <i>Advanced Science,</i> 10, no. 10 (2023) Wiley: https://doi.org/10.1002/advs.202205781.en_US
dc.identifier.digital2023-Santosen_US
dc.identifier.doihttps://doi.org/10.1002/advs.202205781en_US
dc.identifier.urihttps://hdl.handle.net/1911/114815en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleVisible-Light-Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overloaden_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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