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.