Cargando…
Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus
Critically ill patients have higher risk of serious fungal infections, such as invasive aspergillosis (IA) which is mainly caused by the human fungal pathogen Aspergillus fumigatus. Triazole drugs are the primary therapeutic agents for the first-line treatment of IA, which could easily cause drug re...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928863/ https://www.ncbi.nlm.nih.gov/pubmed/36819018 http://dx.doi.org/10.3389/fmicb.2023.1089267 |
_version_ | 1784888729031147520 |
---|---|
author | Du, Wenlong Xu, Ruolin He, Zhiqiang Yang, Huan Gu, Yufan Liu, Yi |
author_facet | Du, Wenlong Xu, Ruolin He, Zhiqiang Yang, Huan Gu, Yufan Liu, Yi |
author_sort | Du, Wenlong |
collection | PubMed |
description | Critically ill patients have higher risk of serious fungal infections, such as invasive aspergillosis (IA) which is mainly caused by the human fungal pathogen Aspergillus fumigatus. Triazole drugs are the primary therapeutic agents for the first-line treatment of IA, which could easily cause drug resistance problems. Here, we assess the potential of AgNPs synthesized with Artemisia argyi leaf extract and domiphen as new antifungal agents to produce synergistic antimicrobial effects on Aspergillus fumigatus, and dissect possible molecular mechanisms of action. Plate inoculation assays combined with drug susceptibility test and cytotoxicity test showed that the combination of AgNPs and domiphen has synergistic antimicrobial effects on A. fumigatus with low cytotoxicity. Gene Ontology (GO) enrichment analysis showed that AgNPs and domiphen inhibit the growth of A. fumigatus by suppressing nitrate assimilation, and purine nucleobase metabolic process and amino acid transmembrane transport, respectively. When the two drugs are combined, AgNPs has epistatic effects on domiphen. Moreover, the combination of AgNPs and domiphen primarily influence secondary metabolites biosynthesis, steroid biosynthesis and nucleotide sugar metabolism of A. fumigatus via Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, protein–protein interactions (PPI) analysis combined with validation experiments showed that the combination of AgNPs and domiphen could enhance the expression of copper transporter and inhibit nitrogen source metabolism. In addition, the synergistic antimicrobial effects could be enhanced or eliminated depending on exogenous addition of copper and nitrogen source, respectively. Taken together, the results of this study provide a theoretical basis and a new strategy for the treatment of IA. |
format | Online Article Text |
id | pubmed-9928863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99288632023-02-16 Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus Du, Wenlong Xu, Ruolin He, Zhiqiang Yang, Huan Gu, Yufan Liu, Yi Front Microbiol Microbiology Critically ill patients have higher risk of serious fungal infections, such as invasive aspergillosis (IA) which is mainly caused by the human fungal pathogen Aspergillus fumigatus. Triazole drugs are the primary therapeutic agents for the first-line treatment of IA, which could easily cause drug resistance problems. Here, we assess the potential of AgNPs synthesized with Artemisia argyi leaf extract and domiphen as new antifungal agents to produce synergistic antimicrobial effects on Aspergillus fumigatus, and dissect possible molecular mechanisms of action. Plate inoculation assays combined with drug susceptibility test and cytotoxicity test showed that the combination of AgNPs and domiphen has synergistic antimicrobial effects on A. fumigatus with low cytotoxicity. Gene Ontology (GO) enrichment analysis showed that AgNPs and domiphen inhibit the growth of A. fumigatus by suppressing nitrate assimilation, and purine nucleobase metabolic process and amino acid transmembrane transport, respectively. When the two drugs are combined, AgNPs has epistatic effects on domiphen. Moreover, the combination of AgNPs and domiphen primarily influence secondary metabolites biosynthesis, steroid biosynthesis and nucleotide sugar metabolism of A. fumigatus via Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, protein–protein interactions (PPI) analysis combined with validation experiments showed that the combination of AgNPs and domiphen could enhance the expression of copper transporter and inhibit nitrogen source metabolism. In addition, the synergistic antimicrobial effects could be enhanced or eliminated depending on exogenous addition of copper and nitrogen source, respectively. Taken together, the results of this study provide a theoretical basis and a new strategy for the treatment of IA. Frontiers Media S.A. 2023-02-01 /pmc/articles/PMC9928863/ /pubmed/36819018 http://dx.doi.org/10.3389/fmicb.2023.1089267 Text en Copyright © 2023 Du, Xu, He, Yang, Gu and Liu. 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 Du, Wenlong Xu, Ruolin He, Zhiqiang Yang, Huan Gu, Yufan Liu, Yi Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus |
title | Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus |
title_full | Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus |
title_fullStr | Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus |
title_full_unstemmed | Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus |
title_short | Transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of AgNPs and Domiphen on the human fungal pathogen Aspergillus fumigatus |
title_sort | transcriptomics-based investigation of molecular mechanisms underlying synergistic antimicrobial effects of agnps and domiphen on the human fungal pathogen aspergillus fumigatus |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928863/ https://www.ncbi.nlm.nih.gov/pubmed/36819018 http://dx.doi.org/10.3389/fmicb.2023.1089267 |
work_keys_str_mv | AT duwenlong transcriptomicsbasedinvestigationofmolecularmechanismsunderlyingsynergisticantimicrobialeffectsofagnpsanddomiphenonthehumanfungalpathogenaspergillusfumigatus AT xuruolin transcriptomicsbasedinvestigationofmolecularmechanismsunderlyingsynergisticantimicrobialeffectsofagnpsanddomiphenonthehumanfungalpathogenaspergillusfumigatus AT hezhiqiang transcriptomicsbasedinvestigationofmolecularmechanismsunderlyingsynergisticantimicrobialeffectsofagnpsanddomiphenonthehumanfungalpathogenaspergillusfumigatus AT yanghuan transcriptomicsbasedinvestigationofmolecularmechanismsunderlyingsynergisticantimicrobialeffectsofagnpsanddomiphenonthehumanfungalpathogenaspergillusfumigatus AT guyufan transcriptomicsbasedinvestigationofmolecularmechanismsunderlyingsynergisticantimicrobialeffectsofagnpsanddomiphenonthehumanfungalpathogenaspergillusfumigatus AT liuyi transcriptomicsbasedinvestigationofmolecularmechanismsunderlyingsynergisticantimicrobialeffectsofagnpsanddomiphenonthehumanfungalpathogenaspergillusfumigatus |