Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli

Abstract

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

Activity of Temporin A and Short Lipopeptides Combined with Gentamicin against Biofilm Formed by Staphylococcus aureus and Pseudomonas aeruginosa

“…The amphibian peptide citropin 1.1 demonstrated synergistic action with rifampin and minocycline against a SA biofilm [ 57 ]. Derivatives of P -113 created by substitution of non-natural amino acid residues restored the antimicrobial activity of vancomycin against vancomycin-resistant E. faecium , SA and wild-type EC [ 58 ].…”

Virulence Characteristics and Antibiotic Resistance Profiles of Shiga Toxin-Producing Escherichia coli Isolates from Diverse Sources

“…The following 17 antibiotics were tested: ampicillin, methicillin, penicillin, vancomycin, erythromycin, clindamycin, ciprofloxacin, chloramphenicol, gentamicin, imipenem, meropenem, streptomycin, tetracycline, kanamycin, nalidixic acid, novobiocin, and tigecycline. E. coli ATCC 25922, which is sensitive to all the drugs, was used as the control strain [6,[36][37][38][39]. The results were used to classify the strains as resistant or susceptible to a specific antibiotic using standard reference values recommended by the CLSI National Committee [35].…”

Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria

“…To evaluate synergistic effects, Wu et al [ 105 ] performed a check-board study with the antimicrobial peptide P-113 and its derivatives against VRE. The following derivatives were developed with phenylalanine-(Phe-P-113), β-naphthylalanine-(Nal-P-113), β-diphenylalanine-(Dip-P-113), and β-(4,4′-biphenyl)alanine-(Bip-P-113)-substituted histidine-rich antimicrobial peptide P-113 (Ac-AKRHHGYKRKFH-NH2).…”