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Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model
Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro. We evaluated the efficacy of...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092556/ https://www.ncbi.nlm.nih.gov/pubmed/33361288 http://dx.doi.org/10.1128/AAC.01874-20 |
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author | Campione, Elena Gaziano, Roberta Doldo, Elena Marino, Daniele Falconi, Mattia Iacovelli, Federico Tagliaferri, Daniela Pacello, Lucrezia Bianchi, Luca Lanna, Caterina Aurisicchio, Luigi Centofanti, Federica Di Francesco, Paolo Del Principe, Ilaria Del Bufalo, Francesca Locatelli, Franco Pistoia, Enrico Salvatore Marra, Emanuele Orlandi, Augusto |
author_facet | Campione, Elena Gaziano, Roberta Doldo, Elena Marino, Daniele Falconi, Mattia Iacovelli, Federico Tagliaferri, Daniela Pacello, Lucrezia Bianchi, Luca Lanna, Caterina Aurisicchio, Luigi Centofanti, Federica Di Francesco, Paolo Del Principe, Ilaria Del Bufalo, Francesca Locatelli, Franco Pistoia, Enrico Salvatore Marra, Emanuele Orlandi, Augusto |
author_sort | Campione, Elena |
collection | PubMed |
description | Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro. We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of subinhibitory concentration of amphotericin B (AmB) and posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to posaconazole. Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal heat shock protein 90 (Hsp90) expression and Hsp90-related genes. ATRA treatment reduced mortality in a model of IPA in vivo. Those findings suggest ATRA as a suitable fungistatic agent that can also reduce dosage and adverse reactions of classical antifungal drugs and add to the development of new therapeutic strategies against IPA and systemic fungal infections. |
format | Online Article Text |
id | pubmed-8092556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80925562021-05-05 Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model Campione, Elena Gaziano, Roberta Doldo, Elena Marino, Daniele Falconi, Mattia Iacovelli, Federico Tagliaferri, Daniela Pacello, Lucrezia Bianchi, Luca Lanna, Caterina Aurisicchio, Luigi Centofanti, Federica Di Francesco, Paolo Del Principe, Ilaria Del Bufalo, Francesca Locatelli, Franco Pistoia, Enrico Salvatore Marra, Emanuele Orlandi, Augusto Antimicrob Agents Chemother Experimental Therapeutics Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro. We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of subinhibitory concentration of amphotericin B (AmB) and posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to posaconazole. Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal heat shock protein 90 (Hsp90) expression and Hsp90-related genes. ATRA treatment reduced mortality in a model of IPA in vivo. Those findings suggest ATRA as a suitable fungistatic agent that can also reduce dosage and adverse reactions of classical antifungal drugs and add to the development of new therapeutic strategies against IPA and systemic fungal infections. American Society for Microbiology 2021-02-17 /pmc/articles/PMC8092556/ /pubmed/33361288 http://dx.doi.org/10.1128/AAC.01874-20 Text en Copyright © 2021 Campione et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Experimental Therapeutics Campione, Elena Gaziano, Roberta Doldo, Elena Marino, Daniele Falconi, Mattia Iacovelli, Federico Tagliaferri, Daniela Pacello, Lucrezia Bianchi, Luca Lanna, Caterina Aurisicchio, Luigi Centofanti, Federica Di Francesco, Paolo Del Principe, Ilaria Del Bufalo, Francesca Locatelli, Franco Pistoia, Enrico Salvatore Marra, Emanuele Orlandi, Augusto Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model |
title | Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus
In Vitro and in a Pulmonary Aspergillosis In Vivo Model |
title_full | Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus
In Vitro and in a Pulmonary Aspergillosis In Vivo Model |
title_fullStr | Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus
In Vitro and in a Pulmonary Aspergillosis In Vivo Model |
title_full_unstemmed | Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus
In Vitro and in a Pulmonary Aspergillosis In Vivo Model |
title_short | Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus
In Vitro and in a Pulmonary Aspergillosis In Vivo Model |
title_sort | antifungal effect of all-trans retinoic acid against aspergillus fumigatus
in vitro and in a pulmonary aspergillosis in vivo model |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092556/ https://www.ncbi.nlm.nih.gov/pubmed/33361288 http://dx.doi.org/10.1128/AAC.01874-20 |
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