Role of OsaA in Aspergillus fumigatus development and virulence

Author:

Ana Calvo-byrd (US)

Abstract:

Objectives: Aspergillus fumigatus is the leading cause of aspergillosis, with high mortality rates particularly in mmunocompromised individuals. In this study we elucidate the role of the transcription factor OsaA in A.fumigatus virulence and morphological and chemical development.
Methods: osaA deletion mutant and overexpression strains were generated for physiological and chemical characterization, as well as for virulence analyses in neutropenic and non-neutropenic mouse models.
Results: In search for novel genetic targets against aspergillosis infections, we studied the WOPR transcription factor OsaA in A. fumigatus. Deletion of osaA results in colony growth reduction with respect to the wild type. Our results revealed that conidiation is also influenced by osaA; both deletion and overexpression of this gene resulted in a decrease in conidial production, particularly in the former. This study also indicated that osaA is necessary for normal cell wall integrity. Furthermore, deletion of osaA resulted in a reduction in the ability of this fungus to adhere to surfaces, thermotolerance, and caused increased sensitivity to oxidative stress. Metabolomics analysis indicated that A. fumigatus osaA deletion or overexpression resulted in alterations in the production of numerous secondary metabolites. Importantly, deletion of osaA resulted in a reduction in mortality rate in neutropenic and in the corticosteroid-immunodepressed mouse models.
Conclusions: Aspergillus fumigatus osaA is indispensable for virulence in the neutropenic and corticosteroid-induced immune-repressed environments. osaA influences growth, development, and sensitivity to environmental stressors, such as oxidative and temperature stresses, which could affect pathogenicity in this fungus. Furthermore, osaA was found to positively regulate the capacity of adhesion to surfaces, an important characteristic for the formation of biofilm. Importantly, this WOPR domain transcription factor gene is also necessary for normal synthesis of secondary metabolites, many of them known to play a role during infection, including gliotoxin. This study suggests that osaA or its product are promising targets with potential to be used in a control strategy against A. fumigatus infections.

Abstract Number: 62

Conference Year: 2024

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