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Recombinant phage displaying ToAP2D peptide with antifungal activity against Sporothrix globosa
Tianyi Yan1, Lin An2, Feng Chen2
1Department of Rehabilitation Medicine, China-Japan Union Hospital of Jilin University, Changchun, China.
Abstract:
We designed and synthesized recombinant phage nanofibers displaying ToAP2D peptide and investigated their antifungal effect on Sporothrix and the corresponding mechanism. Antimicrobial peptide, ToAP2D, was used as the template. The effect of synthesized recombinant phages on the immune function of CD4+ T lymphocytes in mice was tested using an enzyme-linked immunosorbent assay. The therapeutic effect and safety of recombinant phage administration on Sporothrix-infected BALB/c mice were evaluated based on survival analysis, histopathological changes, and renal and liver functions. The successfully prepared recombinant phage displaying ToAP2D peptides significantly inhibited Sporothrix growth. According to the scanning electron microscopy results, the recombinant phage caused shrinkage and rupture of Sporothrix globosa, leading to leakage of the contents. The Hoechst/propidium iodide double staining test indicated that the recombinant phage could induce cell apoptosis of Sporothrix globosa. The apoptotic pathway might be due to the accumulation of reactive oxygen species in large quantities in cells, activating caspase dependence; this reduced inflammation, prolonged the survival time, and enhanced levels of IFN-γ and IL-17 in mice. We believe that recombinant phage inhibits Sporothrix growth by adjusting the immune response of mice, inducing Sporothrix apoptosis and improving animal survival. This study offers a new approach to preparing antimicrobial peptides.
Insights
Recombinant phages displaying ToAP2D peptides effectively inhibit Sporothrix growth by inducing apoptosis and enhancing immune responses. This novel approach offers a promising new strategy for developing antimicrobial peptides against fungal infections.
Area of Science:
- Mycology
- Biotechnology
- Immunology
Background:
- Sporothrix infections pose a significant health challenge.
- Antimicrobial peptides offer potential therapeutic avenues.
- Developing novel delivery systems for antimicrobial agents is crucial.
Purpose of the Study:
- To design and synthesize recombinant phage nanofibers displaying the ToAP2D peptide.
- To investigate the antifungal mechanism of these phages against Sporothrix.
- To evaluate the therapeutic efficacy and safety of recombinant phage administration in a mouse model.
Main Methods:
- Synthesis of recombinant phage nanofibers displaying ToAP2D peptide.
- Antifungal activity assessment using scanning electron microscopy and Hoechst/propidium iodide staining.
- In vivo studies in Sporothrix-infected BALB/c mice, including survival analysis and assessment of immune function (CD4+ T lymphocytes, IFN-γ, IL-17) and organ function.
- Enzyme-linked immunosorbent assay (ELISA) for immune cell analysis.
Main Results:
- Recombinant phages significantly inhibited Sporothrix growth, causing cell shrinkage, rupture, and apoptosis.
- The mechanism involves reactive oxygen species accumulation and caspase-dependent pathways.
- In vivo, recombinant phages reduced inflammation, prolonged survival, and enhanced key immune markers (IFN-γ, IL-17) in infected mice.
- Therapeutic administration showed favorable safety profiles regarding renal and liver functions.
Conclusions:
- Recombinant phage nanofibers displaying ToAP2D peptide are effective against Sporothrix.
- The antifungal action is mediated by direct fungal cell damage and induction of apoptosis.
- The phage therapy modulates the host immune response, improving outcomes in a murine model.
- This study presents a novel method for preparing antimicrobial peptides with therapeutic potential.
