Loading…

Antifungal activity and mode of action of synthetic peptides derived from the tick OsDef2 defensin

Candida albicans is the principal opportunistic fungal pathogen in nosocomial settings and resistance to antifungal drugs is on the rise. Antimicrobial peptides from natural sources are promising novel therapeutics against C. albicans. OsDef2 defensin was previously found to be active against only G...

Full description

Saved in:
Bibliographic Details
Published in:Journal of peptide science 2022-05, Vol.28 (5), p.e3383-n/a
Main Authors: Mbuayama, Kabuzi R., Taute, Helena, Strӧmstedt, Adam A., Bester, Megan J., Gaspar, Anabella R. M.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Candida albicans is the principal opportunistic fungal pathogen in nosocomial settings and resistance to antifungal drugs is on the rise. Antimicrobial peptides from natural sources are promising novel therapeutics against C. albicans. OsDef2 defensin was previously found to be active against only Gram‐positive bacteria, whereas derived fragments Os and its cysteine‐free analogue, Os‐C, are active against Gram‐positive and Gram‐negative bacteria at low micromolar concentrations. In this study, OsDef2‐derived analogues and fragments were screened for anticandidal activity with the aim to identify peptides with antifungal activity and in so doing obtain a better understanding of the structural requirements for activity and modes of action. Os, Os‐C and Os(11–22)NH2, a Os‐truncated carboxy‐terminal‐amidated fragment, had the most significant antifungal activities, with minimum fungicidal concentrations (MFCs) in the micromolar range (6–28 μM). C. albicans killing was rapid and occurred within 30–60 min. Further investigations showed all three peptides interacted with cell wall derived polysaccharides while both Os and Os(11–22)NH2 permeabilized fungal liposomes. Confocal laser scanning microscopy confirmed that Os‐C and Os(11–22)NH2 could enter the cytosol of live cells and subsequent findings suggest that the uptake of Os and Os‐C, in contrast to Os(11–22)NH2, is energy dependent. Although Os, Os‐C and Os(11–22)NH2 induced the production of reactive oxygen species (ROS), co‐incubation with ascorbic acid revealed that only ROS generated by Os‐C and to a lesser extent Os(11–22)NH2 resulted in cell death. Overall, Os, Os‐C and Os(11–22)NH2 are promising candidacidal agents. C‐terminal derivative of OsDef2, Os and shorter derivatives Os‐C and Os(11–22)NH2 are active against Candida albicans.
ISSN:1075-2617
1099-1387
1099-1387
DOI:10.1002/psc.3383