Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment

Bacteremia and associated bacterial sepsis are potentially fatal and occur when the host response to microbial invasion is impaired or compromised. This motivated us to develop carbonized polymer dots (CPDs_Man/AA) from a mixture of mannose (Man) and positively charged amino acids [AAs; lysine, arginine (Arg), or histidine] through a one-step mild pyrolysis procedure, which effectively inhibited drug-resistant bacterial strains isolated from septic patients. The as-prepared CPDs_Man/AA showed broad-spectrum antibacterial activity, including multidrug-resistant bacteria, even in human plasma. The minimal inhibitory concentration of CPDs_Man/Arg is ca. 1.0 μg mL^-1, which is comparable to or lower than those of other tested antibiotics (e.g., ampicillin, gentamicin, and vancomycin). In addition to directly disrupting bacterial membranes, the CPDs_Man/Arg feature a structure similar to aminoglycoside antibiotics that could bind to 16S rRNA, thereby blocking bacterial protein synthesis. In vitro cytotoxic and hemolytic assays demonstrated the high biocompatibility of the CPDs_Man/AA. In addition, in vivo studies on methicillin-resistant Staphylococcus aureus-infected mice treated with the CPDs_Man/Arg showed a significant decrease in mortality-even better than that of antibiotics. Overall, the synthesis of the CPDs_Man/AA is cost-efficient, straightforward, and effective for treating bacteremia. The polymeric features of the CPDs_Man/Arg, including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen our reliance on antibiotics to treat systemic bacterial infections in the future.