Tick defensins may serve as templates for the development of multifunctional peptides. The purpose of this study was to
evaluate shorter peptides derived from tick defensin isoform 2 (OsDef2) in terms of their antibacterial, antioxidant,
and cytotoxic activities. We compared the structural and functional properties of a synthetic peptide derived from the
carboxy-terminal of the parent peptide (Os) to that of an analogue in which the three cysteine residues were omitted
(Os–C). Here, we report that both peptides were bactericidal (MBC values ranging from 0.94–15mg/ml) to both Gram-positive
and Gram-negative bacteria, whereas the parent peptide only exhibited Gram-positive antibacterial activity. The Os peptide
was found to be two-fold more active than Os–C against three of the four tested bacteria but equally active against Staphylococcus
aureus. Os showed rapid killing kinetics against both Escherichia coli and Bacillus subtilis, whereas Os–C took longer,
suggesting different modes of action. Scanning electron microscopy showed that in contrast to melittin for which blebbing
of bacterial surfaces was observed, cells exposed to either peptide appeared flattened and empty. Circular dichroism data
indicated that in a membrane-mimicking environment, the cysteine-containing peptide has a higher a-helical content.
Both peptides were found to be non-toxic to mammalian cells. Moreover, the peptides displayed potent antioxidant activity
and were 12 times more active than melittin. Multifunctional peptides hold potential for a wide range of clinical applications
and further investigation into their mode of antibacterial and antioxidant properties is therefore warranted.