Antimicrobial effect of a novel chitosan derivative and its synergistic effect with antibiotics

Cationic polymers are promising antibacterial agents since they have a low propensity for bacteria to evolve resistance, but they usually have low biocompatibility due to their hydrophobic moieties. Herein, we report a new biodegradable and biocompatible chitosan-derived cationic antibacterial polymer, 2,6-Diamino Chitosan (2,6-DAC). 2,6-DAC shows excellent broad-spectrum antimicrobial activity with minimum inhibitory concentrations (MICs) of 8-32 µg/mL against clinically relevant and multi-drug resistant (MDR) bacteria including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Further, 2,6-DAC shows an excellent synergistic effect with various clinically relevant antibiotics proved by decreasing the MICs of the antibiotics against MDR A. baumannii and MRSA to 2.4 log10 reduction of A. baumannii in murine intraperitoneal and lung infection models. The novel chitosan derivative, 2,6-DAC, can be utilized as biocompatible broad-spectrum cationic antimicrobial agent alone or in synergistic combination with various antibiotics. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Ministry of Health (MOH) Nanyang Technological University Accepted version We thank the funding support from Singapore Ministry of Education Tier 3 grants (MOE2013-T3-1-002, MOE2018-T3-1-003), a Singapore Ministry of Health Industry Alignment Fund (NMRC/ MOHIAFCAT2/003/2014) and NTU. We also thank the ASTAR Wound Care Innovation for the Tropics IAF-PP (HBMS Domain) with grant number H17/01/a0/0M9, and ASTAR RIE2020 Advanced Manufacturing and Engineering (AME) IAP-PP Specialty Chemicals Programme (Grant No. A1786a0032). We also thank the Major Project of 2025 Sci&Tech Innovation of Ningbo (2018B10052) and NSF of China, 8147179.