460nm visible light irradiation eradicates MRSA via inducing prophage activation

A growing number of researches demonstrate that light with a wavelength between 400 and 500nm, namely blue light (BL), has exhibited antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA) and other microbes. However, there is insufficient evidence to show that BL kills MRSA inside biofilm and the mechanisms underlying the antibacterial effects remain unclear. Here we demonstrate that BL irradiation with 460nm effectively eliminated both planktonic and biofilm MRSA in a dose-dependent manner by utilizing a planktonic MRSA or MRSA biofilm model. Furthermore, using a animal model of skin wound infections with MRSA, we found that 460nm BL showed a therapeutic effect on MRSA infected wounds in mice with significant killing of MRSA, better survival and wound healing. Moreover, RNA sequencing was used to analyze differential gene expressions in MRSA genome after BL irradiation. Our data showed that about one third of up-regulated genes were phage-related. Using phage inhibitor GS-11P, increased prophage activation in MRSA cells induced by BL irradiation was blocked and phage particles were observed. The results indicate that blue visible light irradiation with 460nm is a novel tool for eliminating both planktonic and biofilm MRSA. Prophage activation may be involved in the process. This study may provide a new perspective to understand the antibacterial mechanism by BL.