Carbon nanogels exert multipronged attack on resistant bacteria and strongly constrain resistance evolution

Developing antimicrobial agents that can eradicate drug-resistant (DR) bacteria and provide sustained protection from DR bacteria is a major challenge. Herein, we report a mild pyrolysis approach to prepare carbon nanogels (CNGs) through polymerization and the partial carbonization of l-lysine hydrochloride at 270 °C as a potential broad-spectrum antimicrobial agent that can inhibit biopolymer-producing bacteria and clinical drug-resistant isolates and tackle drug resistance issues. We thoroughly studied the structures of the CNGs, their antibacterial mechanism, and biocompatibility. CNGs possess superior bacteriostatic effects against drug-resistant bacteria compared to some commonly explored antibacterial nanomaterials (silver, copper oxide, and zinc oxide nanoparticles, and graphene oxide) through multiple antimicrobial mechanisms, including reactive oxygen species generation, membrane potential dissipation, and membrane function disruption, due to the positive charge and flexible colloidal structures resulting strong interaction with bacterial membrane. The minimum inhibitory concentration (MIC) values of the CNGs (0.6 µg mL^-1 against E. coli and S. aureus) remained almost the same against the bacteria after 20 passages; however, the MIC values increased significantly after treatment with silver nanoparticles, antibiotics, the bacteriostatic chlorhexidine, and especially gentamicin (approximately 140-fold). Additionally, the CNGs showed a negligible MIC value difference against the obtained resistant bacteria after acclimation to the abovementioned antimicrobial agents. The findings of this study unveil the development of antimicrobial CNGs as a sustainable solution to combat multidrug-resistant bacteria.