Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence
<i>Aspergillus fumigatus</i> is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. The deletion of the <i>o...
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MDPI AG
2024-01-01
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| Series: | Journal of Fungi |
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| author | Apoorva Dabholkar Sandesh Pandit Ritu Devkota Sourabh Dhingra Sophie Lorber Olivier Puel Ana M. Calvo |
| author_facet | Apoorva Dabholkar Sandesh Pandit Ritu Devkota Sourabh Dhingra Sophie Lorber Olivier Puel Ana M. Calvo |
| author_sort | Apoorva Dabholkar |
| collection | DOAJ |
| description | <i>Aspergillus fumigatus</i> is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. The deletion of the <i>osaA</i> gene resulted in colony growth reduction. Conidiation is also influenced by <i>osaA</i>; both <i>osaA</i> deletion and overexpression resulted in a decrease in spore production. Wild-type expression levels of <i>osaA</i> are necessary for the expression of the conidiation regulatory genes <i>brlA</i>, <i>abaA</i>, and <i>wetA</i>. In addition, <i>osaA</i> is necessary for normal cell wall integrity. Furthermore, the deletion of <i>osaA</i> resulted in a reduction in the ability of <i>A. fumigatus</i> to adhere to surfaces, decreased thermotolerance, as well as increased sensitivity to oxidative stress. Metabolomics analysis indicated that <i>osaA</i> deletion or overexpression led to alterations in the production of multiple secondary metabolites, including gliotoxin. This was accompanied by changes in the expression of genes in the corresponding secondary metabolite gene clusters. These effects could be, at least in part, due to the observed reduction in the expression levels of the <i>veA</i> and <i>laeA</i> global regulators when the <i>osaA</i> locus was altered. Importantly, our study shows that <i>osaA</i> is indispensable for virulence in both neutropenic and corticosteroid-immunosuppressed mouse models. |
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| publishDate | 2024-01-01 |
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| series | Journal of Fungi |
| spelling | doaj.art-956b468c2e9e4a07afaa22d5fdcb2ee42024-02-23T15:23:26ZengMDPI AGJournal of Fungi2309-608X2024-01-0110210310.3390/jof10020103Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and VirulenceApoorva Dabholkar0Sandesh Pandit1Ritu Devkota2Sourabh Dhingra3Sophie Lorber4Olivier Puel5Ana M. Calvo6Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USADepartment of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USADepartment of Biological Sciences and Eukaryotic Pathogen Innovation Center, Clemson University, Clemson, SC 29634, USADepartment of Biological Sciences and Eukaryotic Pathogen Innovation Center, Clemson University, Clemson, SC 29634, USAToxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, FranceToxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, FranceDepartment of Biological Sciences, Northern Illinois University, DeKalb, IL 60115, USA<i>Aspergillus fumigatus</i> is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. The deletion of the <i>osaA</i> gene resulted in colony growth reduction. Conidiation is also influenced by <i>osaA</i>; both <i>osaA</i> deletion and overexpression resulted in a decrease in spore production. Wild-type expression levels of <i>osaA</i> are necessary for the expression of the conidiation regulatory genes <i>brlA</i>, <i>abaA</i>, and <i>wetA</i>. In addition, <i>osaA</i> is necessary for normal cell wall integrity. Furthermore, the deletion of <i>osaA</i> resulted in a reduction in the ability of <i>A. fumigatus</i> to adhere to surfaces, decreased thermotolerance, as well as increased sensitivity to oxidative stress. Metabolomics analysis indicated that <i>osaA</i> deletion or overexpression led to alterations in the production of multiple secondary metabolites, including gliotoxin. This was accompanied by changes in the expression of genes in the corresponding secondary metabolite gene clusters. These effects could be, at least in part, due to the observed reduction in the expression levels of the <i>veA</i> and <i>laeA</i> global regulators when the <i>osaA</i> locus was altered. Importantly, our study shows that <i>osaA</i> is indispensable for virulence in both neutropenic and corticosteroid-immunosuppressed mouse models.https://www.mdpi.com/2309-608X/10/2/103<i>Aspergillus fumigatus</i>OsaAaspergillosisWOPR domainconidiationsecondary metabolism |
| spellingShingle | Apoorva Dabholkar Sandesh Pandit Ritu Devkota Sourabh Dhingra Sophie Lorber Olivier Puel Ana M. Calvo Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence Journal of Fungi <i>Aspergillus fumigatus</i> OsaA aspergillosis WOPR domain conidiation secondary metabolism |
| title | Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence |
| title_full | Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence |
| title_fullStr | Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence |
| title_full_unstemmed | Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence |
| title_short | Role of the <i>osaA</i> Gene in <i>Aspergillus fumigatus</i> Development, Secondary Metabolism and Virulence |
| title_sort | role of the i osaa i gene in i aspergillus fumigatus i development secondary metabolism and virulence |
| topic | <i>Aspergillus fumigatus</i> OsaA aspergillosis WOPR domain conidiation secondary metabolism |
| url | https://www.mdpi.com/2309-608X/10/2/103 |
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