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Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload
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 population...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074111/ https://www.ncbi.nlm.nih.gov/pubmed/36715588 http://dx.doi.org/10.1002/advs.202205781 |
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author | Santos, Ana L. Beckham, Jacob L. Liu, Dongdong Li, Gang van Venrooy, Alexis Oliver, Antonio Tegos, George P. Tour, James M. |
author_facet | Santos, Ana L. Beckham, Jacob L. Liu, Dongdong Li, Gang van Venrooy, Alexis Oliver, Antonio Tegos, George P. Tour, James M. |
author_sort | Santos, Ana L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10074111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100741112023-04-06 Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload Santos, Ana L. Beckham, Jacob L. Liu, Dongdong Li, Gang van Venrooy, Alexis Oliver, Antonio Tegos, George P. Tour, James M. Adv Sci (Weinh) Research Articles 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. John Wiley and Sons Inc. 2023-01-30 /pmc/articles/PMC10074111/ /pubmed/36715588 http://dx.doi.org/10.1002/advs.202205781 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Santos, Ana L. Beckham, Jacob L. Liu, Dongdong Li, Gang van Venrooy, Alexis Oliver, Antonio Tegos, George P. Tour, James M. Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload |
title | Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload |
title_full | Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload |
title_fullStr | Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload |
title_full_unstemmed | Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload |
title_short | Visible‐Light‐Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload |
title_sort | visible‐light‐activated molecular machines kill fungi by necrosis following mitochondrial dysfunction and calcium overload |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074111/ https://www.ncbi.nlm.nih.gov/pubmed/36715588 http://dx.doi.org/10.1002/advs.202205781 |
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