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Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane
Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly in the cell membrane; one is the classical ion channel model in which AmB vertically forms transmembrane tunnel and the other is a r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787481/ https://www.ncbi.nlm.nih.gov/pubmed/33523971 http://dx.doi.org/10.1126/sciadv.abd5230 |
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author | Dong, Pu-Ting Zong, Cheng Dagher, Zeina Hui, Jie Li, Junjie Zhan, Yuewei Zhang, Meng Mansour, Michael K. Cheng, Ji-Xin |
author_facet | Dong, Pu-Ting Zong, Cheng Dagher, Zeina Hui, Jie Li, Junjie Zhan, Yuewei Zhang, Meng Mansour, Michael K. Cheng, Ji-Xin |
author_sort | Dong, Pu-Ting |
collection | PubMed |
description | Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly in the cell membrane; one is the classical ion channel model in which AmB vertically forms transmembrane tunnel and the other is a recently proposed sterol sponge model where AmB is laterally adsorbed onto the membrane surface. To address this controversy, we use polarization-sensitive stimulated Raman scattering from fingerprint C═C stretching vibration to visualize AmB, ergosterol, and lipid in single fungal cells. Intracellular lipid droplet accumulation in response to AmB treatment is found. AmB is located in membrane and intracellular droplets. In the 16 strains studied, AmB residing inside cell membrane was highly ordered, and its orientation is primarily parallel to phospholipid acyl chains, supporting the ion channel model. Label-free imaging of AmB and chemical contents offers an analytical platform for developing low-toxicity, resistance-refractory antifungal agents. |
format | Online Article Text |
id | pubmed-7787481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77874812021-01-14 Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane Dong, Pu-Ting Zong, Cheng Dagher, Zeina Hui, Jie Li, Junjie Zhan, Yuewei Zhang, Meng Mansour, Michael K. Cheng, Ji-Xin Sci Adv Research Articles Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly in the cell membrane; one is the classical ion channel model in which AmB vertically forms transmembrane tunnel and the other is a recently proposed sterol sponge model where AmB is laterally adsorbed onto the membrane surface. To address this controversy, we use polarization-sensitive stimulated Raman scattering from fingerprint C═C stretching vibration to visualize AmB, ergosterol, and lipid in single fungal cells. Intracellular lipid droplet accumulation in response to AmB treatment is found. AmB is located in membrane and intracellular droplets. In the 16 strains studied, AmB residing inside cell membrane was highly ordered, and its orientation is primarily parallel to phospholipid acyl chains, supporting the ion channel model. Label-free imaging of AmB and chemical contents offers an analytical platform for developing low-toxicity, resistance-refractory antifungal agents. American Association for the Advancement of Science 2021-01-06 /pmc/articles/PMC7787481/ /pubmed/33523971 http://dx.doi.org/10.1126/sciadv.abd5230 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Dong, Pu-Ting Zong, Cheng Dagher, Zeina Hui, Jie Li, Junjie Zhan, Yuewei Zhang, Meng Mansour, Michael K. Cheng, Ji-Xin Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane |
title | Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane |
title_full | Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane |
title_fullStr | Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane |
title_full_unstemmed | Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane |
title_short | Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane |
title_sort | polarization-sensitive stimulated raman scattering imaging resolves amphotericin b orientation in candida membrane |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787481/ https://www.ncbi.nlm.nih.gov/pubmed/33523971 http://dx.doi.org/10.1126/sciadv.abd5230 |
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