Screening and transcriptomic analysis of anti-Sporothrix globosa targeting AbaA

Ying Wang¹Xiaoyan Wu²Xiyuan Fan¹Chanxu Han²Fangliang Zheng^1*Zhenying Zhang^2,3*

• ¹Liaoning University, Shenyang, China
• ²Department of Dermatology, Shenzhen Hospital, The University of Hong Kong, Shenzhen, Guangdong Province, China
• ³Department of Dermatology, The eighth affiliated hospital, SUN YAT-SEN University, Shenzhen, China

Sporotrichosis is a fungal disease caused by a complex of Sporothrix schenckii, leading to chronic infections of the epidermis and subcutaneous tissue in both humans and animals. The emergence of drug-resistant strains in sporotrichosis has highlighted the urgent need to identify new drug targets. In this study, we measured growth curves, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) for both Sporothrix globosa (S. globosa) and Sporothrix schenckii (S. schenckii). The results confirmed that both Azelastine and Mefloquine significantly inhibited the growth of these fungi. Additionally, animal experiments demonstrated that these drugs reduced skin lesions in mice, and post-treatment observations revealed improvements in inflammatory infiltration and granuloma formation. In conclusion, Azelastine and Mefloquine exhibit the potential to inhibit Sporothrix and treat sporotrichosis both in vitro and in murine models, they may inhibit fungal growth by binding to a crucial fungal target, the AbaA protein, or by modulating the host's immune response, suggesting their potential as therapeutic agents for this condition. Furthermore, we utilized bioinformatics to predict virulence factors regulated by the abaA gene. Through transcriptome analysis and qRT-PCR for validation, our findings demonstrate that the abaA gene plays a crucial role in regulating the attachment of the Sporothrix cell wall to the host matrix and in melanin regulation. Notably, when the abaA gene was inhibited, there was a marked increase in the expression of repair genes. These results emphasize the significance of the abaA gene in the biology of Sporothrix.