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

• Main Authors: Chih-Lung Wu, Ju-Yun Hsueh, Bak-Sau Yip, Ya-Han Chih, Kuang-Li Peng, Jya-Wei Cheng
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: International Journal of Molecular Sciences
• Subjects: antimicrobial peptide; antibiotic resistance; vancomycin; synergism; bulky non-nature amino acid
• Online Access: https://www.mdpi.com/1422-0067/21/13/4578
• ISSN: 1661-6596; 1422-0067

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 <i>Enterococcus faecium, Staphylococcus aureus</i>, and wild-type <i>Escherichia coli</i>. 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 <i>E. coli</i> 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.