Dual Antibacterial Activities and Biofilm Eradication of a Marine Peptide-N6NH 2 and Its Analogs against Multidrug-Resistant Aeromonas veronii .

Aeromonas veronii is one of the main pathogens causing various diseases in humans and animals. It is currently difficult to eradicate drug-resistant A. veronii due to the biofilm formation by conventional antibiotic treatments. In this study, a marine peptide-N6NH ₂ and its analogs were generated by introducing Orn or replacing with D-amino acids, Val and Pro; their enzymic stability and antibacterial/antibiofilm ability against multi-drug resistant (MDR) A. veronii ACCC61732 were detected in vitro and in vivo, respectively. The results showed that DN6NH ₂ more rapidly killed A. veronii ACCC61732 and had higher stability in trypsin, simulated gastric/intestinal fluid, proteinase K, and mouse serum than the parent peptide-N6NH ₂ . DN6NH ₂ and other analogs significantly improved the ability of N6NH ₂ to penetrate the outer membrane of A. veronii ACCC61732. DN6NH ₂ , N6PNH ₂ and V112N6NH ₂ protected mice from catheter-associated biofilm infection with MDR A. veronii ACCC61732, superior to N6NH ₂ and CIP. DN6NH ₂ had more potent efficacy at a dose of 5 μmol/kg (100% survival) in a mouse peritonitis model than other analogs (50-66.67%) and CIP (83.33%), and it inhibited the bacterial translocation, downregulated pro-inflammatory cytokines, upregulated the anti-inflammatory cytokine, and ameliorated multiple-organ injuries (including the liver, spleen, lung, and kidney). These data suggest that the analogs of N6NH ₂ may be a candidate for novel antimicrobial and antibiofilm agents against MDR A. veronii infections.