Synergistic effect and antibiofilm activity of an antimicrobial peptide with traditional antibiotics against multi-drug resistant bacteria

Combined treatment of AMPs with classical antibiotics has gained interest because it often results in a synergistic antibacterial effect. We demonstrated here that Pt5-1c, an AMP derived from phosvitin, had antibacterial activity against the MDR bacteria (S. aureus USA500, E. coli 577 and K. pneumoniae 2182) in the presence of serum. On this basis, we showed that Pt5-1c was synergistically active with traditional antibiotics (oxacillin, vancomycin, streptomycin and azithromycin) against the three MDR bacteria growing as biofilms in vitro and in vivo. Moreover, Pt5-1c restored sensitivity of S. aureus USA500 to oxacillin and vancomycin, E. coli 577 to streptomycin and K. pneumoniae 2182 to azithromycin. Importantly, long-term exposure to Pt5-1c did not give rise to antimicrobial resistance. Collectively, these data not only suggest a promising combinatorial therapy strategy to combat antibiotics-tolerant infections but also present a possibility of Pt5-1c being used to prolong the application of antibiotics including oxacillin, vancomycin, streptomycin and azithromycin, that are under threat of becoming ineffective due to antibiotic resistance.