Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides

Abstract

IntroductionAs the development of new antimicrobial agents faces a historical decline, the issue of bacterial drug resistance has become a serious dilemma that threatens the human population worldwide. Antimicrobial peptides (AMPs) represent an attractive and a promising class of antimicrobial agents.AimThe hybridization of AMPs aimed at merging two individual active fragments of native peptides to generate a new AMP with altered physicochemical properties that translate into an enhanced safety profile.Materials and methodsIn this study, we have rationally designed a new hybrid peptide via combining two individual α-helical fragments of both BMAP-27 and OP-145. The resultant peptide, was evaluated for its antimicrobial and antibiofilm activity against a range of microbial strains. The resultant peptide was also evaluated for its toxicity against mammalian cells using hemolytic and anti proliferative assays.ResultsThe antimicrobial activity of H4 revealed that the peptide is displaying a broad spectrum of activity against both Gram-positive and Gram-negative bacteria including standard and multidrug-resistant bacterial strains in the range of 2.5–25 μM. The new hybrid peptide displayed potent activity in eradicating biofilm-forming cells, and the reported minimum biofilm eradication concentrations were equal to the minimum inhibitory concentration values reported for planktonic cells. Additionally, H4 exhibited reduced toxicity profiles against eukaryotic cells. Combining H4 peptide with conventional antibiotics has led to a dramatic enhancement of the antimicrobial activity of both agents with synergistic or additive outcomes.ConclusionOverall, this study indicates the success of both the hybridization and synergism strategy in developing AMPs as potential antimicrobial therapeutics with reduced toxicity profiles that could be efficiently employed to eradicate resistant bacterial strains and enhance the selectivity and toxicity profiles of native AMPs.

Antimicrobial Activity of Protein Fraction from Naja ashei Venom against Staphylococcus epidermidis

“…The antibacterial effect of ampicillin is based on the inhibition of penicillin-binding proteins involved in cell wall synthesis, whereas tetracycline inhibits 30S subunit during protein synthesis [46]. In general, FIC smaller than MIC makes the protein or peptide factor less toxic and the antibiotic more effective at lower concentrations [44,47]. The mechanism of the creation of synergy is explained in many ways.…”

In vivo antimicrobial activity of the hybrid peptide H4: a follow-up study

“… 8 We have recently reported the design of a novel hybrid peptide AMP named H4 by merging two individual α-helical fragments from two predefined native peptides. 9 This hybridization strategy managed to reduce hemolytic and mammalian cell toxicity of the resultant synthetic peptide (H4) significantly, while achieving potent antimicrobial activity against standard and multi-drug resistant bacterial strains. H4 is capable of eliminating the growth of multi-drug resistant bacteria with minimum inhibitory concentration values as low as 5 µM.…”

Computational screening of antimicrobial peptides for Acinetobacter baumannii

“…Since data availability was limited, we had to include data from different groups. AMP sequence and activity data against A. Baumannii was curated from different sources [42–52] and is presented in Table A in S1 File. The curated AMP data set had the activity of 75 AMPs with their length ranging from 10 to 43 amino acids and charges in the range +1 to +12.…”