Tryptophan end-tagging confers antifungal activity to a tick-derived antimicrobial peptide

<p dir="ltr">These datasets consist of quantitative and qualitative data from the analysis of the antifungal activity of Os-C and Os-C(W₅) including circular dichroism spectra, snapshots and graphs of <i>in silico</i> molecular dynamics simulations, fluorecescence readings of cell viability assasy, absorbance readings indicating the biomass reducing effects of Os-C(W₅), light microscopy images indicating the effect of Os-C(W₅) on biofilm formation and scanning electron microscopy images indicating the effect of Os-C(W₅) on the <i>C. albicans</i> morphology. </p><p dir="ltr">Mechanistic insight into the structural characteristics of Os-C(W₅) compared with Os-C is provided by circular dichroism (CD) spectroscopy and molecular dynamics (MD) simulations. Steady state analysis using CD spectroscopy shows that tryptophan end-tagging alters the secondary structure in Tris buffer and sodium dodecyl sulfate. <i>In silico</i>, MD simulations of peptides were performed with a <i>C. albicans</i> model membrane consisting of the lipids 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoethanolamine (POPE), 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoinositol (POPI), 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phospho-L-serine (POPS) and ergosterol. Like the CD data, MD simulation data reveals changes in the secondary structure of Os-C after end-tagging. Furthermore, MD simulations show that tryptophan end-tagging reduces interactions with and insertion into a model <i>C. albicans</i> membrane and promotes peptide aggregation at its surface.</p><p dir="ltr">Antiplanktonic assays indicate that tryptophan end-tagging enhances the activity of Os-C which decreases the growth and viability of <i>C. albicans</i>. More in-depth mode of action studies reveal that Os-C(W₅) does not cause membrane permeabilisation. Instead, the antifungal activity correlates with the induction of reactive oxygen species and changes in cell morphology.</p><p dir="ltr">Further antibiofilm studies show that Os-C(W₅) prevents biofilm formation and eradicates preformed biofilms. Reduced cell adhesion and viability contribute to reduced biofilm extracellular matrix formation. Although reduced, Os-C(W₅) retains some antibiofilm activity in RPMI-1640 supplemented with 50% foetal bovine serum and in a synthetic wound medium.</p><p dir="ltr">In conclusion, this study demonstrates that tryptophan end-tagging is a simple modification that transforms a salt-sensitive AMP (Os-C) into a peptide (Os-C(W₅)) with antifungal activity in physiologically relevant environments.</p>