Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i>
<i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) is a filamentous fungus that causes invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. This study found that deleting the guanine nucleotide exchan...
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2025-01-01
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| author | Yuhuan Liu Shumi Shang Cong Liu Yichen Liu Keyang Xu Dan He Li Wang |
| author_facet | Yuhuan Liu Shumi Shang Cong Liu Yichen Liu Keyang Xu Dan He Li Wang |
| author_sort | Yuhuan Liu |
| collection | DOAJ |
| description | <i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) is a filamentous fungus that causes invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. This study found that deleting the guanine nucleotide exchange factor <i>Sec2p</i> gene led to slower <i>A. fumigatus</i> growth and reduced the fungal burden and mortality of infected mice. However, the mechanism by which this gene affects <i>A. fumigatus</i> growth and pathogenicity remains unclear. Transmission electron microscopy revealed that the vacuoles of the gene knockout strain <i>ΔSec2p</i> accumulated more autophagosomes, indicating inhibition of autophagosome degradation. When phenylmethylsulfonyl fluoride was applied to inhibit autophagosome degradation, the <i>ΔSec2p</i> strain produced fewer autophagosomes; the <i>ΔSec2p</i> autophagy pathway was inhibited, affecting <i>A. fumigatus</i>’ nutrient homeostasis and growth. Unlike the wild type, the <i>ΔSec2p</i> strain showed strong resistance to cell wall stress. When exposed to caspofungin, <i>Sec2p</i> negatively regulated the expression of cell wall integrity (CWI) pathway genes and participated in the cell wall stress response of <i>A. fumigatus</i>. Furthermore, this gene positively regulated the autophagy pathway and enhanced CWI pathway gene expression to respond to rapamycin-induced autophagy. In summary, <i>Sec2p</i> positively regulated the autophagy pathway; it negatively regulated the CWI pathway during cell wall stress, coordinating the growth and pathogenicity of <i>A. fumigatus</i>. |
| format | Article |
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| institution | Kabale University |
| issn | 2309-608X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Journal of Fungi |
| spelling | doaj-art-8d31bae9ddab4f5ea402a8b067bd50a22025-01-24T13:37:18ZengMDPI AGJournal of Fungi2309-608X2025-01-011113610.3390/jof11010036Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i>Yuhuan Liu0Shumi Shang1Cong Liu2Yichen Liu3Keyang Xu4Dan He5Li Wang6Department of Pathogenobiology, Jilin University Mycology Research Center, Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogenobiology, Jilin University Mycology Research Center, Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, ChinaDepartment of Pathogenobiology, Jilin University Mycology Research Center, Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogenobiology, Jilin University Mycology Research Center, Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogenobiology, Jilin University Mycology Research Center, Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathogenobiology, Jilin University Mycology Research Center, Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, China<i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) is a filamentous fungus that causes invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. This study found that deleting the guanine nucleotide exchange factor <i>Sec2p</i> gene led to slower <i>A. fumigatus</i> growth and reduced the fungal burden and mortality of infected mice. However, the mechanism by which this gene affects <i>A. fumigatus</i> growth and pathogenicity remains unclear. Transmission electron microscopy revealed that the vacuoles of the gene knockout strain <i>ΔSec2p</i> accumulated more autophagosomes, indicating inhibition of autophagosome degradation. When phenylmethylsulfonyl fluoride was applied to inhibit autophagosome degradation, the <i>ΔSec2p</i> strain produced fewer autophagosomes; the <i>ΔSec2p</i> autophagy pathway was inhibited, affecting <i>A. fumigatus</i>’ nutrient homeostasis and growth. Unlike the wild type, the <i>ΔSec2p</i> strain showed strong resistance to cell wall stress. When exposed to caspofungin, <i>Sec2p</i> negatively regulated the expression of cell wall integrity (CWI) pathway genes and participated in the cell wall stress response of <i>A. fumigatus</i>. Furthermore, this gene positively regulated the autophagy pathway and enhanced CWI pathway gene expression to respond to rapamycin-induced autophagy. In summary, <i>Sec2p</i> positively regulated the autophagy pathway; it negatively regulated the CWI pathway during cell wall stress, coordinating the growth and pathogenicity of <i>A. fumigatus</i>.https://www.mdpi.com/2309-608X/11/1/36<i>Aspergillus fumigatus</i><i>Sec2p</i>growthautophagycell wallvirulence |
| spellingShingle | Yuhuan Liu Shumi Shang Cong Liu Yichen Liu Keyang Xu Dan He Li Wang Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i> Journal of Fungi <i>Aspergillus fumigatus</i> <i>Sec2p</i> growth autophagy cell wall virulence |
| title | Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i> |
| title_full | Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i> |
| title_fullStr | Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i> |
| title_full_unstemmed | Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i> |
| title_short | Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i> |
| title_sort | roles of the i sec2p i gene in the growth and pathogenicity regulation of i aspergillus fumigatus i |
| topic | <i>Aspergillus fumigatus</i> <i>Sec2p</i> growth autophagy cell wall virulence |
| url | https://www.mdpi.com/2309-608X/11/1/36 |
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