Selectively Antibacterial Action of Deoxy Cationic Cellulose for Effectively Killing ESKAPE Bacteria

Efficiently eradicating superbacteria without harming normal cells and inducing bacterial drug-resistance holds significant importance in safeguarding human health. Herein, we discovered a novel selective bactericidal material synthesized from natural cellulose as the backbone, with cationic groups introduced via a deoxygenation process. Compared to conventional ester-type cationic cellulose derivatives (CCDs), deoxy-type CCDs exhibit high selective bactericidal activity. Through tailored cationic structure and substitution degree modulation, these derivatives achieve targeted bacterial eradication at low concentrations while maintaining mammalian cell biocompatibility. Specifically, deoxy-type CCDs, C-Ts-BenA0.80 and C-Ts-TBuP0.83, demonstrate minimum inhibitory concentrations (MICs) of 16 μg/mL and 4 μg/mL against E. coli and S. aureus, respectively, with corresponding selectivity indices of 312 and 50. Deoxy-type CCDs have strong cell-membrane depolarization ability owing to the unique surface charge distribution, thus leading to bacterial death. Based on the physical membrane-disruption mechanism, deoxy-type CCDs do not induce the emergence of drug-resistant bacteria and can effectively kill a variety of superbugs, including ESKAPE bacteria. The synergistic effect between the linkage bond and cations offers a new approach for constructing highly efficient and nontoxic inactivating materials.