Antibacterial activity of synthetic peptide W5(Os-C) against Staphylococcus epidermidis ATCC 35984

Abstract

Antimicriobial resistant Staphylococcus epidermidis infections are rapidly increasing. A promising research avenue is the use of antimicrobial peptides (AMPs). From AMP OsDef2, C-terminal fragments Os and Os-C were generated, but activity loss in physiological salt environments limits clinical applications. As an attempt to increase the antimicrobial activity under these conditions, Os-C was tagged on the N-terminal with five tryptophan residues. The minimum inhibitory concentrations (MICs) for the anti-planktonic activity of W5(Os-C) (W), vancomycin (V), and combination ratios 3V:1W and 2V:2W were 2.44 µM, 3.83 µM, 3.31 µM and 3.63 µM respectively. The biofilm inhibition concentrations (BICs) of W5(Os-C), vancomycin, and combination ratios 3V:1W and 2V:2W were 3.81 µM, 3.06 µM, 3.48 µM and 4.51 µM respectively for cell viability, and 3.76 µM, 3.07 µM, 6.68 µM and 4.40 µM respectively for biomass inhibition. Antimicrobial combinations failed to achieve synergism. In silico studies revealed that W5(Os-C) formed dimers or trimers and inserted into a model Gram-positive membrane regardless of salt concentration. Peptide-peptide interactions in a physiological salt environment were both hydrophilic and hydrophobic, but mainly hydrophobic in a higher salt environment. Irrespective of salt concentration, W5(Os-C) inserted into the Gram-positive model membrane via the N-terminal tryptophan tag but inserted deeper in the higher salt environment. In conclusion, N-terminal tagging of Os-C with tryptophan residues increases the anti-planktonic and biofilm inhibitory activity, mediated by dimer/trimer formation and N-terminal insertion into S. epidermidis model membranes.