Near-infrared anti-microbial therapy: eliminating MRSA by bleaching of STX

Methicillin-resistant Staphylococcus aureus (MRSA) caused invasive infection is a major public health problem primarily related to hospitals or other healthcare settings. However, traditional antibiotics were no longer effective enough because of the ability of pathogens to continuously develop antibiotic resistances. In order to find alternatives in treating MRSA infections, scientists targeted on a goldencolored pigment Staphyloxanthin (STX) located on most of S. aureus membrane, which is one of the virulence factor that help MRSA evade from antibiotic toxicity. Getting rid of STX was proved to sensitize MRSA against drugs including β-lactam antibiotics. Delightfully, both direct inhibition of STX expression and indirect blue light photobleaching of STX were proved to be effective in eradication MRSA in vitro and in vivo. However, protein inhibition took too long time to work, and had off-targeting and cell toxicity issue; and blue light photolysis can hardly be effective into the soft tissue layer of human skin for treating invasive infections because of the limitation in its penetration depth. This thesis illustrates a NIR light illuminating method in STX bleaching, opening a new window for invasive MRSA treatment. According to our results, NIR light was proved to effectively break down STX molecule in a wide range of wavelength, and induce synergistical effect with H2O2 in eradicating planktonic MRSA. H2O2 was to produce reactive oxygen species (ROS) that can disturb the cellular oxidative environment and induce cell death. Moreover, fresh porcine skin was applied to demonstrate the potential penetration depth of NIR laser and STX photolysis effciency through a thick turbid skin tissue. Colony forming unit was conducted to verify the bacterial killing effciency. Resonant Raman spectroscopy was used for quantification of the STX photolysis by characteristic Raman peaks. Different laser systems were applied for particular purposes: femto-second laser with fixed wavelength was used for fast bleaching and power dependent tests, and nano-second laser with tunable wavelength was chosen for wavelength dependent experiments. To illustrate the NIR photo-bleaching mechanism, more mysterious findings were presented which need us to uncover in the future. Considering the host immune response in generateing ROS in defending MRSA infections, in the future, either impairing antioxidant systems or enhancing the endogenous levels of ROS in bacteria could be useful strategies to increase oxidative damage onto pathogens.2022-01-28T00:00:00