Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus aureus infection both inv itro and in vivo.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most common multi-drug resistant bacteria in both hospital and community. The aim of this study is to investigate the selective inhibition of MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a quencher molecule to two side chains of cephalosporin, which was then shown to have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed yields of fluorescence quantum and singlet oxygen. The selective inactivation and less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and confirmed by conducting PDT to two Staphylococcus aureus strains and human skin cells at a fluence of 15 J/cm(2) with 640±10 nm LED light. Furthermore, using mouse skin wound model infected with 10(8) CFU of MRSA, we found that both LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound repair. However, there was no significant difference in the two photosensitizers that might be due to the environment in vivo. Modification of the photosensitizer will be very beneficial for developing new strategies to treat drug resistant bacterial infection with less harm to host tissue.