Role of the osaA Gene in Aspergillus fumigatus Development, Secondary Metabolism and Virulence

被引:3
作者
Dabholkar, Apoorva [1 ]
Pandit, Sandesh [1 ]
Devkota, Ritu [2 ,3 ]
Dhingra, Sourabh [2 ,3 ]
Lorber, Sophie [4 ]
Puel, Olivier [4 ]
Calvo, Ana M. [1 ]
机构
[1] Northern Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA
[2] Clemson Univ, Dept Biol Sci, Clemson, SC 29634 USA
[3] Clemson Univ, Eukaryot Pathogen Innovat Ctr, Clemson, SC 29634 USA
[4] Univ Toulouse, Toxalim Res Ctr Food Toxicol, ENVT, INRAE,INP-Purpan,UPS, F-31027 Toulouse, France
关键词
Aspergillus fumigatus; OsaA; aspergillosis; WOPR domain; conidiation; secondary metabolism; virulence; CONIDIAL PIGMENT BIOSYNTHESIS; CELL TRANSPLANT RECIPIENTS; COLONY-STIMULATING FACTOR; INVASIVE ASPERGILLOSIS; PULMONARY ASPERGILLOSIS; GLIOTOXIN PRODUCTION; CYTOKINE PRODUCTION; PATHOGENESIS; REGULATOR; IDENTIFICATION;
D O I
10.3390/jof10020103
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Aspergillus fumigatus 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 osaA gene resulted in colony growth reduction. Conidiation is also influenced by osaA; both osaA deletion and overexpression resulted in a decrease in spore production. Wild-type expression levels of osaA are necessary for the expression of the conidiation regulatory genes brlA, abaA, and wetA. In addition, osaA is necessary for normal cell wall integrity. Furthermore, the deletion of osaA resulted in a reduction in the ability of A. fumigatus to adhere to surfaces, decreased thermotolerance, as well as increased sensitivity to oxidative stress. Metabolomics analysis indicated that osaA 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 veA and laeA global regulators when the osaA locus was altered. Importantly, our study shows that osaA is indispensable for virulence in both neutropenic and corticosteroid-immunosuppressed mouse models.
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页数:20
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