AUTHOR=Yan Tianyi , An Lin , Chen Feng 

TITLE=Recombinant phage displaying ToAP2D peptide with antifungal activity against Sporothrix globosa

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1022651

DOI=10.3389/fphar.2022.1022651

ISSN=1663-9812

ABSTRACT=<p>We designed and synthesized recombinant phage nanofibers displaying ToAP2D peptide and investigated their antifungal effect on <italic>Sporothrix</italic> and the corresponding mechanism. Antimicrobial peptide, ToAP2D, was used as the template. The effect of synthesized recombinant phages on the immune function of CD4<sup>+</sup> T lymphocytes in mice was tested using an enzyme-linked immunosorbent assay. The therapeutic effect and safety of recombinant phage administration on <italic>Sporothrix</italic>-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 <italic>Sporothrix</italic> growth. According to the scanning electron microscopy results, the recombinant phage caused shrinkage and rupture of <italic>Sporothrix globosa</italic>, leading to leakage of the contents. The Hoechst/propidium iodide double staining test indicated that the recombinant phage could induce cell apoptosis of <italic>Sporothrix globosa</italic>. 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 <italic>Sporothrix</italic> growth by adjusting the immune response of mice, inducing <italic>Sporothrix</italic> apoptosis and improving animal survival. This study offers a new approach to preparing antimicrobial peptides.</p>