Abstract
In recent years methicillin-resistant Staphylococcus aureus has posed a challenge in treating skin and soft tissue infections. Finding new antimicrobial agents has therefore become imperative. We evaluated the in vitro antimicrobial activity of a synthetic peptide, P6, against multidrug resistant clinical strains of Staphylococcus aureus isolated from skin and soft tissue infections. The P6 antimicrobial effect was evaluated in vitro by determining MIC/MBC, the ratio of live/dead cells and the effects induced at membrane level. The therapeutic efficiency was determined against human skin cells. P6 inhibited growth for all strains between 8 and 16 mg/L and killed all bacterial strains at 16 mg/L. The therapeutic potential was found to be 30 and 15 in the presence of BSA. We showed that P6 localizes at membrane level, where it acts slowly, by depolarizing it and affecting its integrity. P6 can be considered a good candidate for use as an antimicrobial agent in topical applications.
Highlights
Computational Physics and Information Technologies, “Horia Hulubei” National Institute of Physics and Nuclear Engineering, Măgurele, Romania. 4“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania. *email: Strain code A1 A2 A3 A4 A5 A6 A7 A8 A9 A10 Reference strain (ATCC 6538)
For all strains the bacteriostatic effect was observed at concentrations between 8 and 16 mg/L, to the results previously obtained on the reference strain[20]
The toxicity on skin cells is reduced as compared with the toxicity we previously reported against human lymphocytes[20], resulting a therapeutic index of ~30 that is in line with Therapeutic Index (TI) reported by previous studies regarding the effects of short arginine and/or tryptophan rich peptides[16,18], TI varying between 16 and 128 depending on the bacterial strain
Summary
Antimicrobial peptides (AMP) are recognized as a promising class of substances having high potential for biotechnological applications. Their particular physical features (negative charge, hydrophobicity, etc) allow for specific mechanisms of action, mainly damaging the bacterial membrane[12]. In a recent report we proposed a synthetic short tryptophan and arginine rich peptide as a candidate for antimicrobial approaches[20]. The peptide (namely P6, structure HRWWRWWRR) proved good efficiency against Gram negative and positive bacterial strains (including S. aureus). In this study we investigated the antimicrobial effect of P6 on several multidrug resistant clinical strains of Staphylococcus aureus isolated from skin and soft tissue infections. In accordance with our results, a possible action mechanism is outlined, future clinical applications were considered
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