Antimicrobial Effect of a Novel Chitosan Derivative and Its Synergistic Effect with Antibiotics

• DOI: 10.1021/acsami.0c20881
• Publication Date: 2021-01-08T03:11:05Z
• Authors: Zhangyong Si; Zheng Hou; Yogesh Shankar Vikhe; Kishore Reddy Ven...; Kalisvar Marimuthu; Partha Pratim De; Oon Tek Ng; Peng Li; Yabin Zhu; Kevin Pethe; Mary B. Chan-Park
• Keywords: Methicillin-Resistant Staphylococcus aureus; Chitosan; Mice, Inbred BALB C; Bacteria; Chitosan Derivatives; Drug Synergism; Bacterial Infections; Microbial Sensitivity Tests; 02 engineering and technology; :Chemical engineering::Polymers and polymer manufacture [Engineering]; Anti-Bacterial Agents; 3. Good health; Antibacterial; Animals; Humans; Female; 0210 nano-technology

Cationic polymers are promising antibacterial agents because bacteria have a low propensity to develop resistance against them, but they usually have low biocompatibility because of 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 multidrug-resistant (MDR) bacteria including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Furthermore, 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 methicillin-resistant Staphylococcus aureus to <1 μg/mL. In vivo biocompatibility of 2,6-DAC is proved by a dosage of 100 mg/kg compound via oral administration and 25 mg/kg compound via intraperitoneal injection to mice; 2,6-DAC does not cause any weight loss and any significant change in liver and kidney biomarkers or the important blood electrolytes. The combinations of 2,6-DAC together with novobiocin and rifampicin show >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 a biocompatible broad-spectrum cationic antimicrobial agent alone or in synergistic combination with various antibiotics.