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Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans
Cryptococcus neoformans is the leading cause of cryptococcosis, an invasive and potentially fatal infectious disease. Therapeutic failures are due to the increase in antifungal resistance, the adverse effects of drugs, and the unavailability of therapeutic regimens in low-income countries, which lim...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222688/ https://www.ncbi.nlm.nih.gov/pubmed/34177839 http://dx.doi.org/10.3389/fmicb.2021.660645 |
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author | Andriani, Gabriella Maria Morguette, Ana Elisa Belotto Spoladori, Laís Fernanda Almeida Pereira, Patrícia Morais Lopes Cabral, Weslei Roberto Correia Fernandes, Bruna Terci Tavares, Eliandro Reis Almeida, Ricardo Sérgio Lancheros, Cesar Armando Contreras Nakamura, Celso Vataru Mello, João Carlos Palazzo Yamauchi, Lucy Megumi Yamada-Ogatta, Sueli Fumie |
author_facet | Andriani, Gabriella Maria Morguette, Ana Elisa Belotto Spoladori, Laís Fernanda Almeida Pereira, Patrícia Morais Lopes Cabral, Weslei Roberto Correia Fernandes, Bruna Terci Tavares, Eliandro Reis Almeida, Ricardo Sérgio Lancheros, Cesar Armando Contreras Nakamura, Celso Vataru Mello, João Carlos Palazzo Yamauchi, Lucy Megumi Yamada-Ogatta, Sueli Fumie |
author_sort | Andriani, Gabriella Maria |
collection | PubMed |
description | Cryptococcus neoformans is the leading cause of cryptococcosis, an invasive and potentially fatal infectious disease. Therapeutic failures are due to the increase in antifungal resistance, the adverse effects of drugs, and the unavailability of therapeutic regimens in low-income countries, which limit the treatment of cryptococcosis, increasing the morbidity and mortality associated with these infections. Thus, new antifungal drugs and innovative strategies for the cryptococcosis treatment are urgently needed. The aim of the present study was to evaluate the effect of ethyl acetate fraction (EAF) of Poincianella pluviosa stem bark on planktonic and biofilm mode of growth of C. neoformans. Furthermore, the interaction between the EAF and amphotericin B (AmB) was evaluated in vitro and in Galleria mellonella infection model. Minimal inhibitory concentrations (MICs) of EAF ranged from 125.0 to >1,000.0 μg/ml and >1,000.0 μg/ml for planktonic and sessile cells, respectively. The combination between EAF and AmB exhibited a synergistic fungicidal activity toward C. neoformans, with a fractional inhibitory concentration index (FICI) ranging from 0.03 to 0.06 and 0.08 to 0.28 for planktonic and sessile cells, respectively. Microscopy analyses of planktonic C. neoformans cells treated with EAF, alone or combined with AmB, revealed morphological and ultrastructural alterations, including loss of integrity of the cell wall and cell membrane detachment, suggesting leakage of intracellular content, reduction of capsule size, and presence of vacuoles. Moreover, EAF alone or combined with AmB prolonged the survival rate of C. neoformans-infected G. mellonella larvae. These findings indicate that P. pluviosa may be an important source of new compounds that can be used as a fungus-specific adjuvant for the treatment of cryptococcosis. |
format | Online Article Text |
id | pubmed-8222688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82226882021-06-25 Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans Andriani, Gabriella Maria Morguette, Ana Elisa Belotto Spoladori, Laís Fernanda Almeida Pereira, Patrícia Morais Lopes Cabral, Weslei Roberto Correia Fernandes, Bruna Terci Tavares, Eliandro Reis Almeida, Ricardo Sérgio Lancheros, Cesar Armando Contreras Nakamura, Celso Vataru Mello, João Carlos Palazzo Yamauchi, Lucy Megumi Yamada-Ogatta, Sueli Fumie Front Microbiol Microbiology Cryptococcus neoformans is the leading cause of cryptococcosis, an invasive and potentially fatal infectious disease. Therapeutic failures are due to the increase in antifungal resistance, the adverse effects of drugs, and the unavailability of therapeutic regimens in low-income countries, which limit the treatment of cryptococcosis, increasing the morbidity and mortality associated with these infections. Thus, new antifungal drugs and innovative strategies for the cryptococcosis treatment are urgently needed. The aim of the present study was to evaluate the effect of ethyl acetate fraction (EAF) of Poincianella pluviosa stem bark on planktonic and biofilm mode of growth of C. neoformans. Furthermore, the interaction between the EAF and amphotericin B (AmB) was evaluated in vitro and in Galleria mellonella infection model. Minimal inhibitory concentrations (MICs) of EAF ranged from 125.0 to >1,000.0 μg/ml and >1,000.0 μg/ml for planktonic and sessile cells, respectively. The combination between EAF and AmB exhibited a synergistic fungicidal activity toward C. neoformans, with a fractional inhibitory concentration index (FICI) ranging from 0.03 to 0.06 and 0.08 to 0.28 for planktonic and sessile cells, respectively. Microscopy analyses of planktonic C. neoformans cells treated with EAF, alone or combined with AmB, revealed morphological and ultrastructural alterations, including loss of integrity of the cell wall and cell membrane detachment, suggesting leakage of intracellular content, reduction of capsule size, and presence of vacuoles. Moreover, EAF alone or combined with AmB prolonged the survival rate of C. neoformans-infected G. mellonella larvae. These findings indicate that P. pluviosa may be an important source of new compounds that can be used as a fungus-specific adjuvant for the treatment of cryptococcosis. Frontiers Media S.A. 2021-06-10 /pmc/articles/PMC8222688/ /pubmed/34177839 http://dx.doi.org/10.3389/fmicb.2021.660645 Text en Copyright © 2021 Andriani, Morguette, Spoladori, Pereira, Cabral, Fernandes, Tavares, Almeida, Lancheros, Nakamura, Mello, Yamauchi and Yamada-Ogatta. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Andriani, Gabriella Maria Morguette, Ana Elisa Belotto Spoladori, Laís Fernanda Almeida Pereira, Patrícia Morais Lopes Cabral, Weslei Roberto Correia Fernandes, Bruna Terci Tavares, Eliandro Reis Almeida, Ricardo Sérgio Lancheros, Cesar Armando Contreras Nakamura, Celso Vataru Mello, João Carlos Palazzo Yamauchi, Lucy Megumi Yamada-Ogatta, Sueli Fumie Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans |
title | Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans |
title_full | Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans |
title_fullStr | Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans |
title_full_unstemmed | Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans |
title_short | Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans |
title_sort | antifungal combination of ethyl acetate extract of poincianella pluviosa (dc.) l. p. queiros stem bark with amphotericin b in cryptococcus neoformans |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222688/ https://www.ncbi.nlm.nih.gov/pubmed/34177839 http://dx.doi.org/10.3389/fmicb.2021.660645 |
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