Screening and transcriptomic analysis of anti- targeting AbaA.

INTRODUCTION

Sporotrichosis is a fungal disease caused by a complex of , leading to chronic infections of the epidermis and subcutaneous tissue in both humans and animals.

METHODS

Through virtual screening targeting the key gene A to screen out the small-molecule drugs to treat Sporotrichosis. To further validate the antifungal activity of small-molecule drugs, growth curves, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) for () and () were measured. In addition, we have done animal experiments to explore the function of the drugs. At the same time, qRT-PCR and transcriptome were used to verify the important role of A gene in .

RESULTS

Azelastine and Mefloquine effectively inhibit S. globosa and S. schenckii. MBC, and MIC for and confirmed that both Azelastine and Mefloquine inhibited the growth of and . Additionally, animal experiments demonstrated that Azelastine and Mefloquine reduced skin lesions in mice; post-treatment observations revealed improvements in inflammatory infiltration and granuloma formation. Through transcriptome analysis and qRT-PCR for validation, our findings demonstrate that the A gene plays a crucial role in regulating the attachment of the cell wall to the host matrix and in melanin regulation. Notably, when the A gene was inhibited, there was a marked increase in the expression of repair genes. These results emphasize the significance of the A gene in the biology of .

DISCUSSION

Two small-molecule drugs exhibit the ability to inhibit and treat sporotrichosis both in vitro and in murine models, suggesting their potential for development as therapeutic agents for sporotrichosis. And qRT-PCR and transcriptome results underscore the significance of the A gene in . Our results lay the foundation for the search for new treatments for other mycosis.