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 Sporothrix globosa, among which ToAP2D had the strongest anti-fungal activity. ToAP2D showed good serum stability without acute toxicity. The ToAP2D treatment inhibited the growth of S. globosa 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 S. globosa. The levels of mitochondrial membrane potential were decreased and that of the reactive oxygen species (ROS) were increased in S. globosa upon ToAP2D treatment. Moreover, ToAP2D activated metacaspase. In the in vivo study, we further demonstrated that ToAP2D inhibited the S. globosa 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.
Highlights
Sporotrichosis is a subcutaneous mycotic infection, which causes localized cutaneous and even severe systemic disseminated infections, and its global incidence increases every year (Etchecopaz et al, 2021)
When the concentration increased to 2 mg/ml and 4 mg/ml, they both showed antifungal activities against S. globosa, and the noticeable inhibition zone diameter was at 4 mg/ml
We further determined that the minimal inhibitory concentration (MIC) of the ToAP2D against S. globosa by the microdilution assay was 156.25 μg/ml
Summary
Sporotrichosis is a subcutaneous mycotic infection, which causes localized cutaneous and even severe systemic disseminated infections, and its global incidence increases every year (Etchecopaz et al, 2021). An epidemiologic study found that approximately 1.6 million people die from fungal infections in the world each year (Struyfs et al, 2021a), and a global increase in sporotrichosis incidence occurs every year, especially in the tropical and subtropical regions (Chakrabarti et al, 2015). Current therapies to treat sporotrichosis are very limited, which mainly include antifungal drugs, photodynamic therapy, thermotherapy, cryotherapy, and surgery, and the effects are still far from satisfactory (Honse et al, 2010; MF Matos et al, 2020; Soeiro Sampaio et al, 2020). Antimicrobial peptides (AMPs) are commonly found in natural organisms, and they have a wide range of functions, including anti-pathogens (Stariha and McCafferty, 2021; Chang et al, 2021; Kim et al, 2021; Sabia Junior et al, 2019), anti-cancer (Rubin and Qvit, 2020), and immune regulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
