Broad-Spectrum Antimicrobial Polymer with Dual Bactericidal Mechanisms Enhances Antibiotic Activity in the Treatment of Fish Infections

Bacterial infection in aquaculture farming has been a well-known issue, and the situation is worsened by the limitations on antibiotic usage due to environmental considerations. This study reports the design and synthesis of a broad-spectrum antimicrobial polymer, P_C3–8, demonstrated for the first time as an efficient antimicrobial agent against a number of common fish pathogens, including Gram-positive and Gram-negative ones. A dual-bactericidal mechanism is proposed for P_C3–8, in which the cationic polymer is found to disrupt bacterial membranes and interact with genome DNA, effectively causing bacterial cell death. P_C3–8 is capable of eliminating pathogens in mammalian cell cultures, preventing them from being killed by those pathogens. When P_C3–8 was applied into water, it healed bacteria-infected zebrafish, outperforming common antibiotics, such as Kanamycin and Chloramphenicol. Importantly, P_C3–8 possesses low drug resistance emergence and potent synergistic effects with commercial antibiotics. Therefore, it shows great effectiveness against resistant pathogens and evades any potential environmental risk related to resistance generation. The present study demonstrates that P_C3–8 is a promising antimicrobial agent for treating bacterial infection related fish diseases and has potential applications in the aquaculture industry.