Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells.
Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A...
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| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3272003?pdf=render |
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| author | Thierry Gauthier Xiaodi Wang Joice Sifuentes Dos Santos Athanasios Fysikopoulos Souria Tadrist Cécile Canlet Marie Pierre Artigot Nicolas Loiseau Isabelle P Oswald Olivier Puel |
| author_facet | Thierry Gauthier Xiaodi Wang Joice Sifuentes Dos Santos Athanasios Fysikopoulos Souria Tadrist Cécile Canlet Marie Pierre Artigot Nicolas Loiseau Isabelle P Oswald Olivier Puel |
| author_sort | Thierry Gauthier |
| collection | DOAJ |
| description | Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC₅₀ close to 7 µM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H₂O₂). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported. |
| first_indexed | 2024-12-10T04:04:06Z |
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| id | doaj.art-6d36f2aedcc048e68bb1438d317917e4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T04:04:06Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6d36f2aedcc048e68bb1438d317917e42022-12-22T02:02:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e2990610.1371/journal.pone.0029906Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells.Thierry GauthierXiaodi WangJoice Sifuentes Dos SantosAthanasios FysikopoulosSouria TadristCécile CanletMarie Pierre ArtigotNicolas LoiseauIsabelle P OswaldOlivier PuelInhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC₅₀ close to 7 µM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H₂O₂). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported.http://europepmc.org/articles/PMC3272003?pdf=render |
| spellingShingle | Thierry Gauthier Xiaodi Wang Joice Sifuentes Dos Santos Athanasios Fysikopoulos Souria Tadrist Cécile Canlet Marie Pierre Artigot Nicolas Loiseau Isabelle P Oswald Olivier Puel Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. PLoS ONE |
| title | Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. |
| title_full | Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. |
| title_fullStr | Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. |
| title_full_unstemmed | Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. |
| title_short | Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. |
| title_sort | trypacidin a spore borne toxin from aspergillus fumigatus is cytotoxic to lung cells |
| url | http://europepmc.org/articles/PMC3272003?pdf=render |
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