The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence
In this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated A. fumigatus uncov...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1327299/full |
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| author | Xabier Guruceaga Uxue Perez-Cuesta Adela Martin-Vicente Eduardo Pelegri-Martinez Harrison I. Thorn Harrison I. Thorn Saioa Cendon-Sanchez Jinhong Xie Jinhong Xie Ashley V. Nywening Ashley V. Nywening Ashley V. Nywening Andoni Ramirez-Garcia Jarrod R. Fortwendel Jarrod R. Fortwendel Aitor Rementeria |
| author_facet | Xabier Guruceaga Uxue Perez-Cuesta Adela Martin-Vicente Eduardo Pelegri-Martinez Harrison I. Thorn Harrison I. Thorn Saioa Cendon-Sanchez Jinhong Xie Jinhong Xie Ashley V. Nywening Ashley V. Nywening Ashley V. Nywening Andoni Ramirez-Garcia Jarrod R. Fortwendel Jarrod R. Fortwendel Aitor Rementeria |
| author_sort | Xabier Guruceaga |
| collection | DOAJ |
| description | In this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated A. fumigatus uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published in vivo transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the maiA gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of maiA resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of β-glucans within the cell wall but did not show lack of chitin or mannans. The maiA-1 mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the A. fumigatus maiA gene to fungal cell wall homeostasis and virulence. |
| first_indexed | 2024-03-08T11:28:28Z |
| format | Article |
| id | doaj.art-ed608cd0adf649ad8318efe5f7449234 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-08T11:28:28Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-ed608cd0adf649ad8318efe5f74492342024-01-26T04:49:35ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-01-011410.3389/fcimb.2024.13272991327299The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulenceXabier Guruceaga0Uxue Perez-Cuesta1Adela Martin-Vicente2Eduardo Pelegri-Martinez3Harrison I. Thorn4Harrison I. Thorn5Saioa Cendon-Sanchez6Jinhong Xie7Jinhong Xie8Ashley V. Nywening9Ashley V. Nywening10Ashley V. Nywening11Andoni Ramirez-Garcia12Jarrod R. Fortwendel13Jarrod R. Fortwendel14Aitor Rementeria15Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Immunology, Microbiology, and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, SpainDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Immunology, Microbiology, and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, SpainDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United StatesGraduate Program in Pharmaceutical Science, College of Graduate Health Sciences, University of Tennessee Healths Science Center, Memphis, TN, United StatesDepartment of Immunology, Microbiology, and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, SpainDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United StatesGraduate Program in Pharmaceutical Science, College of Graduate Health Sciences, University of Tennessee Healths Science Center, Memphis, TN, United StatesDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United StatesIntegrated Program in Biomedical Sciences, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Immunology, Microbiology, and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, SpainDepartment of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Microbiology, Immunology, and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Immunology, Microbiology, and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, SpainIn this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated A. fumigatus uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published in vivo transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the maiA gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of maiA resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of β-glucans within the cell wall but did not show lack of chitin or mannans. The maiA-1 mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the A. fumigatus maiA gene to fungal cell wall homeostasis and virulence.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1327299/fullAspergillus fumigatusmicroarraymaiAcell wallvirulence |
| spellingShingle | Xabier Guruceaga Uxue Perez-Cuesta Adela Martin-Vicente Eduardo Pelegri-Martinez Harrison I. Thorn Harrison I. Thorn Saioa Cendon-Sanchez Jinhong Xie Jinhong Xie Ashley V. Nywening Ashley V. Nywening Ashley V. Nywening Andoni Ramirez-Garcia Jarrod R. Fortwendel Jarrod R. Fortwendel Aitor Rementeria The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence Frontiers in Cellular and Infection Microbiology Aspergillus fumigatus microarray maiA cell wall virulence |
| title | The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence |
| title_full | The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence |
| title_fullStr | The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence |
| title_full_unstemmed | The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence |
| title_short | The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence |
| title_sort | aspergillus fumigatus maia gene contributes to cell wall homeostasis and fungal virulence |
| topic | Aspergillus fumigatus microarray maiA cell wall virulence |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1327299/full |
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