Background and purpose: Antimicrobial resistance toward antibiotics is reaching historical unprecedented levels. There is an urgent and imminent need to develop novel antimicrobial alternatives. Antimicrobial peptides could prove to be a successful group of antimicrobials for drug development. Recently, we have designed a novel synthetic peptide named AamAP1-Lysine. The peptide displayed potent wide-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria. The purpose of this study is to evaluate the antimicrobial effect of combining AamAP1-Lysine with five different conventional antibiotics each representing a distinct mechanism of action in order to explore the possibility of producing a synergistic mode of action against a resistant strain of Gram-positive and a resistant strain of Gram-negative bacteria. Methodology: The antimicrobial activity of AamAP1-Lysine in combination with five different antibiotics were evaluated for their antimicrobial activity employing standard antimicrobial assays, the synergistic activity of the peptide-antibiotic combinations were evaluated using checkerboard technique in addition to real-time time-kill assays. For the antibiofilm studies, the MBEC values were determined by employing the Calgary device. Results: The combination strategy displayed potent synergistic activities against planktonic bacteria in a significant number of peptide-antibiotic combinations. The synergistic activity managed to reduce the effective minimum inhibitory concentration (MIC) concentrations dramatically with some combinations exhibiting a 64-fold decrease in the effective MIC of AamAP1-Lysine individually. Additionally, the combined synergistic activities of the peptide antibiotics were evaluated, and our results have identified two peptide antibiotic combinations with potent synergistic activities against biofilm growing strains of resistant bacteria. Conclusion: Our results clearly indicate that peptide-antibiotic combinations could prove to be a very effective strategy in combatting multidrug-resistant bacteria and biofilm caused infections.
Keywords: AamAP1-Lysine; antibiofilm; antimicrobial peptides; bacterial resistance; synergy.