Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus
In the realm of aspergillosis, a critical concern for immunocompromised patients facing Aspergillus fumigatus, effective management hinges on understanding fungal growth, stress resistance, and response to antifungal treatments. Our study investigates the crucial role of fungal plasma membrane proto...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-02-01
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| Series: | Mycology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21501203.2024.2354273 |
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| author | Chengrui Tan Shaojie Jiang Hongli Zhai Qingwen Hu Chenxi Liu Yi Sun Lujuan Gao |
| author_facet | Chengrui Tan Shaojie Jiang Hongli Zhai Qingwen Hu Chenxi Liu Yi Sun Lujuan Gao |
| author_sort | Chengrui Tan |
| collection | DOAJ |
| description | In the realm of aspergillosis, a critical concern for immunocompromised patients facing Aspergillus fumigatus, effective management hinges on understanding fungal growth, stress resistance, and response to antifungal treatments. Our study investigates the crucial role of fungal plasma membrane proton ATPase (PMA) in nutrient absorption, intertwined with growth and antifungal susceptibility. We employed a high-throughput knockout method to create the PMA gene knockout mutant, ΔAfu-PMA1, in A. fumigatus, alongside a complementation strain. Antifungal susceptibility to triazoles was assessed by micro-dilution method and E-test, revealing decreased sensitivity to voriconazole in ΔAfu-PMA1. Comparative analysis demonstrated significant growth differences, with wild-type strain surpassing ΔAfu-PMA1 by 3.2-fold. Under oxidative stress and heightened osmotic pressure, ΔAfu-PMA1 showed notable growth defects. Loss of PMA led to increased ergosterol and decreased ATP content, alongside pH changes in the culture medium. Transcriptome sequencing unveiled revealed a reduced expression of genes associated with ribosome function, the MAPK pathway, endoplasmic reticulum, and the transport and metabolism of fats, sugars, and proteins in ΔAfu-PMA1, highlighting PMA’s regulatory role in growth and adaptation. These findings emphasise PMA as a potential target for future antifungal drugs, offering hope in combating aspergillosis. |
| format | Article |
| id | doaj-art-a48d6ce6a5914fb98e8152a0a970e820 |
| institution | Kabale University |
| issn | 2150-1203 2150-1211 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Mycology |
| spelling | doaj-art-a48d6ce6a5914fb98e8152a0a970e8202025-02-06T12:16:59ZengTaylor & Francis GroupMycology2150-12032150-12112025-02-0111310.1080/21501203.2024.2354273Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatusChengrui Tan0Shaojie Jiang1Hongli Zhai2Qingwen Hu3Chenxi Liu4Yi Sun5Lujuan Gao6Department of Gastroenterology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, ChinaDepartment of Gastroenterology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, ChinaHealth Science Center, Yangtze University, Jingzhou, ChinaHealth Science Center, Yangtze University, Jingzhou, ChinaHealth Science Center, Yangtze University, Jingzhou, ChinaDepartment of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, ChinaDepartment of Dermatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, ChinaIn the realm of aspergillosis, a critical concern for immunocompromised patients facing Aspergillus fumigatus, effective management hinges on understanding fungal growth, stress resistance, and response to antifungal treatments. Our study investigates the crucial role of fungal plasma membrane proton ATPase (PMA) in nutrient absorption, intertwined with growth and antifungal susceptibility. We employed a high-throughput knockout method to create the PMA gene knockout mutant, ΔAfu-PMA1, in A. fumigatus, alongside a complementation strain. Antifungal susceptibility to triazoles was assessed by micro-dilution method and E-test, revealing decreased sensitivity to voriconazole in ΔAfu-PMA1. Comparative analysis demonstrated significant growth differences, with wild-type strain surpassing ΔAfu-PMA1 by 3.2-fold. Under oxidative stress and heightened osmotic pressure, ΔAfu-PMA1 showed notable growth defects. Loss of PMA led to increased ergosterol and decreased ATP content, alongside pH changes in the culture medium. Transcriptome sequencing unveiled revealed a reduced expression of genes associated with ribosome function, the MAPK pathway, endoplasmic reticulum, and the transport and metabolism of fats, sugars, and proteins in ΔAfu-PMA1, highlighting PMA’s regulatory role in growth and adaptation. These findings emphasise PMA as a potential target for future antifungal drugs, offering hope in combating aspergillosis.https://www.tandfonline.com/doi/10.1080/21501203.2024.2354273Aspergillus fumigatusinvasive aspergillosisplasma membrane proton ATPaseantifungal drug resistancevoriconazolePMA knockout mutant |
| spellingShingle | Chengrui Tan Shaojie Jiang Hongli Zhai Qingwen Hu Chenxi Liu Yi Sun Lujuan Gao Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus Mycology Aspergillus fumigatus invasive aspergillosis plasma membrane proton ATPase antifungal drug resistance voriconazole PMA knockout mutant |
| title | Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus |
| title_full | Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus |
| title_fullStr | Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus |
| title_full_unstemmed | Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus |
| title_short | Exploring the role and mechanisms of the PMA gene in Aspergillus fumigatus |
| title_sort | exploring the role and mechanisms of the pma gene in aspergillus fumigatus |
| topic | Aspergillus fumigatus invasive aspergillosis plasma membrane proton ATPase antifungal drug resistance voriconazole PMA knockout mutant |
| url | https://www.tandfonline.com/doi/10.1080/21501203.2024.2354273 |
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