Metabolic incorporation of ROS-generating cascade-reaction containers in bacterial cell walls for infection control

Bacterial infection has been regarded as a major threat to public health due to multidrug resistant bacteria. Antibiotics still serve as the first-line medications for treating bacterial infections. While excessive and unreasonable use of antibiotics have caused substantially increase in antibiotic-resistance. Therefore, it is significant to develop non-antibiotic-based infection-control strategies to treat bacterial infections without inducing bacterial resistance. Reactive oxygen species (ROS) generated through cascade reaction chemistry, exhibit broad-spectrum antibacterial activity and does not induce bacterial resistance. However, the amount of ROS generated is generally low and antimicrobial efficacies reported are still far from < 3–4 log units necessary for clinical efficacy. Increasing the amounts of ROS generated by adding more substrate may cause collateral tissue damage surrounding an infection site, a risk that may be prevented by locally increasing substrate concentrations. In this thesis magnetic targeting cascade-reaction containers have been developed, which target and accumulate in infectious biofilms to generate ROS inside the biofilm and showed an efficient killing of the bacteria. Cascade-reaction containers were also incorporated inside bacterial cell walls through metabolic labeling to yield long-term presence of ROS, despite the short lifetime (nanoseconds) of individual ROS molecules. These different methods improved the killing efficacy of ROS-generating cascade-reaction containers as a non-antibiotic-based infection-control strategy, against bacterial infection in an infectious biofilm or bacterial pathogen itself.