Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatmentf

摘要

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 acidsAAs;lysine,arginine(Arg),or histidinethrough 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.