Antifungal Effect of All- trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model.

Autor:	Campione E; Dermatologic Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy elena.campione@uniroma2.it., Gaziano R; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy., Doldo E; Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Marino D; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy., Falconi M; Department of Biology, University of Rome Tor Vergata, Rome, Italy., Iacovelli F; Department of Biology, University of Rome Tor Vergata, Rome, Italy., Tagliaferri D; Takis S.r.l., Rome, Italy., Pacello L; Takis S.r.l., Rome, Italy., Bianchi L; Dermatologic Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy., Lanna C; Dermatologic Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy., Aurisicchio L; Takis S.r.l., Rome, Italy., Centofanti F; Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Di Francesco P; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy., Del Principe I; Department of Haematology, University of Rome Tor Vergata, Rome, Italy., Del Bufalo F; Department of Haematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital (IRCSS), Rome, Italy., Locatelli F; Department of Haematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital (IRCSS), Rome, Italy., Pistoia ES; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy., Marra E; Takis S.r.l., Rome, Italy., Orlandi A; Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2021 Feb 17; Vol. 65 (3). Date of Electronic Publication: 2021 Feb 17 (Print Publication: 2021).
DOI:	10.1128/AAC.01874-20
Abstrakt:	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. (Copyright © 2021 Campione et al.)
Databáze:	MEDLINE
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