The Inhibitory Effect of Validamycin A on Aspergillus flavus
Aspergillus flavus is one of the most common isolates from patients with fungal infections. Aspergillus infection is usually treated with antifungal agents, but side effects of these agents are common. Trehalase is an essential enzyme involved in fungal metabolism, and the trehalase inhibitor, valid...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | International Journal of Microbiology |
| Online Access: | http://dx.doi.org/10.1155/2020/3972415 |
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| author | Napasawan Plabutong Supanuch Ekronarongchai Nattarika Niwetbowornchai Steven W. Edwards Sita Virakul Direkrit Chiewchengchol Arsa Thammahong |
| author_facet | Napasawan Plabutong Supanuch Ekronarongchai Nattarika Niwetbowornchai Steven W. Edwards Sita Virakul Direkrit Chiewchengchol Arsa Thammahong |
| author_sort | Napasawan Plabutong |
| collection | DOAJ |
| description | Aspergillus flavus is one of the most common isolates from patients with fungal infections. Aspergillus infection is usually treated with antifungal agents, but side effects of these agents are common. Trehalase is an essential enzyme involved in fungal metabolism, and the trehalase inhibitor, validamycin A, has been used to prevent fungal infections in agricultural products. In this study, we observed that validamycin A significantly increased trehalose levels in A. flavus conidia and delayed germination, including decreased fungal adherence. In addition, validamycin A and amphotericin B showed a combinatorial effect on A. flavus ATCC204304 and clinical isolates with high minimum inhibitory concentrations (MICs) of amphotericin B using checkerboard assays. We observed that validamycin A and amphotericin B had a synergistic effect on A. flavus strains resistant to amphotericin B. The MICs in the combination of validamycin A and amphotericin B were at 0.125 μg/mL and 2 μg/mL, respectively. The FICI of validamycin A and amphotericin B of these clinical isolates was about 0.25–0.28 with synergistic effects. No drug cytotoxicity was observed in human bronchial epithelial cells treated with validamycin A using LDH-cytotoxicity assays. In conclusion, this study demonstrated that validamycin A inhibited the growth of A. flavus and delayed conidial germination. Furthermore, the combined effect of validamycin A with amphotericin B increased A. flavus killing, without significant cytotoxicity to human bronchial epithelial cells. We propose that validamycin A could potentially be used in vivo as an alternative treatment for A. flavus infections. |
| format | Article |
| id | doaj-art-7ba2c87524c040e8a9d740ffde97c7c5 |
| institution | Kabale University |
| issn | 1687-918X 1687-9198 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Microbiology |
| spelling | doaj-art-7ba2c87524c040e8a9d740ffde97c7c52025-02-03T01:28:17ZengWileyInternational Journal of Microbiology1687-918X1687-91982020-01-01202010.1155/2020/39724153972415The Inhibitory Effect of Validamycin A on Aspergillus flavusNapasawan Plabutong0Supanuch Ekronarongchai1Nattarika Niwetbowornchai2Steven W. Edwards3Sita Virakul4Direkrit Chiewchengchol5Arsa Thammahong6Medical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, ThailandMedical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, ThailandMedical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, ThailandInstitute of Integrative Biology, University of Liverpool, Liverpool, UKDepartment of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, ThailandMedical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, ThailandMedical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, ThailandAspergillus flavus is one of the most common isolates from patients with fungal infections. Aspergillus infection is usually treated with antifungal agents, but side effects of these agents are common. Trehalase is an essential enzyme involved in fungal metabolism, and the trehalase inhibitor, validamycin A, has been used to prevent fungal infections in agricultural products. In this study, we observed that validamycin A significantly increased trehalose levels in A. flavus conidia and delayed germination, including decreased fungal adherence. In addition, validamycin A and amphotericin B showed a combinatorial effect on A. flavus ATCC204304 and clinical isolates with high minimum inhibitory concentrations (MICs) of amphotericin B using checkerboard assays. We observed that validamycin A and amphotericin B had a synergistic effect on A. flavus strains resistant to amphotericin B. The MICs in the combination of validamycin A and amphotericin B were at 0.125 μg/mL and 2 μg/mL, respectively. The FICI of validamycin A and amphotericin B of these clinical isolates was about 0.25–0.28 with synergistic effects. No drug cytotoxicity was observed in human bronchial epithelial cells treated with validamycin A using LDH-cytotoxicity assays. In conclusion, this study demonstrated that validamycin A inhibited the growth of A. flavus and delayed conidial germination. Furthermore, the combined effect of validamycin A with amphotericin B increased A. flavus killing, without significant cytotoxicity to human bronchial epithelial cells. We propose that validamycin A could potentially be used in vivo as an alternative treatment for A. flavus infections.http://dx.doi.org/10.1155/2020/3972415 |
| spellingShingle | Napasawan Plabutong Supanuch Ekronarongchai Nattarika Niwetbowornchai Steven W. Edwards Sita Virakul Direkrit Chiewchengchol Arsa Thammahong The Inhibitory Effect of Validamycin A on Aspergillus flavus International Journal of Microbiology |
| title | The Inhibitory Effect of Validamycin A on Aspergillus flavus |
| title_full | The Inhibitory Effect of Validamycin A on Aspergillus flavus |
| title_fullStr | The Inhibitory Effect of Validamycin A on Aspergillus flavus |
| title_full_unstemmed | The Inhibitory Effect of Validamycin A on Aspergillus flavus |
| title_short | The Inhibitory Effect of Validamycin A on Aspergillus flavus |
| title_sort | inhibitory effect of validamycin a on aspergillus flavus |
| url | http://dx.doi.org/10.1155/2020/3972415 |
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