Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa

Abstract

Improving clinical efficacy and reducing treatment time have been the focus of sporotrichosis therapy. Antimicrobial peptides ToAP2A, ToAP2C, and ToAP2D were synthesized on the basis of ToAP2 (AP02759), a peptide derived from the antimicrobial peptide database by the database filtering technology, and their physicochemical characteristics were analyzed. Compared with template peptide ToAP2, the modified peptides had much shorter length, lower molecular weight but significantly greater stability, which in return resulted in increases in the aliphatic index, hydrophilicity, and protein binding ability. Here, we show that the three derived peptides inhibit the growth of <i>Sporothrix globosa</i>, among which ToAP2D had the strongest anti-fungal activity. ToAP2D showed good serum stability without acute toxicity. The ToAP2D treatment inhibited the growth of <i>S. globosa</i> and enhanced apoptosis, which was evidenced by the upregulation of apoptosis-related protein caspase-3. The scanning electron microscopy analysis revealed deformation and rupture of <i>S. globosa</i>. The levels of mitochondrial membrane potential were decreased and that of the reactive oxygen species (ROS) were increased in <i>S. globosa</i> upon ToAP2D treatment. Moreover, ToAP2D activated metacaspase. In the <i>in vivo</i> study, we further demonstrated that ToAP2D inhibited the <i>S. globosa</i> infection of mice footpads, and its efficiency was nearly comparable to itraconazole. In summary, our results suggest that antimicrobial peptide ToAP2D has the potential for sporotrichosis therapy.