Fabulous combination therapy: Synergistic antibiotic inhibition of aquatic antibiotic-resistant bacteria via membrane damage and DNA binding by novel nano antimicrobial peptide C-I20

Aquatic microbiota' antibiotic resistance undermines traditional treatment efficacy, posing a severe threat to sustainable water environment. Our study addresses this challenge through a fantastic approach involving novel nano antimicrobial peptide C-I20 and antibiotics. Antibacterial tests demonstrated that C-I20 effectively combated both standard and aquatic pathogenic resistant strains. C-I20 killed drug-resistant bacteria by disrupting membrane structure and binding to DNA. C-I20 bound to DNA, forming precipitates susceptible to rapid degradation by trypsin and DNase I. When combined with chloramphenicol, florfenicol, ampicillin, or enrofloxacin, C-I20 exhibited remarkably higher inhibitory rates against bacteria compared to individual use of C-I20 or antibiotics alone. Continuous passage analysis revealed that co-administration of C-I20 with chloramphenicol, florfenicol, ampicillin, and enrofloxacin delays the emergence and progression of antibiotic resistance. This combination therapy was proved to be highly effective, notably reducing tissue bacterial loads and pathological changes. Evaluation in an Aeromonas hydrophila infection model showed the lowest morbidity rate and bacterial loading in the C-I20 combined with ampicillin group. Antimicrobial susceptibility analysis confirmed that C-I20 supplementation markedly suppresses ampicillin-induced intestinal resistant bacteria. In conclusion, C-I20 in conjunction with antibiotic therapy effectively inhibits infection and drug-resistant bacterial development, offering a promising strategy for managing drug-resistant bacteria in aquatic animals. [Display omitted] •C-I20 significantly inhibits the development of bacterial resistance.•C-I20 + antibiotics effectively kills drug-resistant bacteria in vitro and in vivo.•C-I20 synergistically kills drug-resistant bacteria with antibiotics.•C-I20 can destroy drug-resistant bacterial membranes and bind to DNA.