Abstract

With the effectiveness of antimicrobials declining as antimicrobial resistance continues to threaten public health, we must look to alternative strategies for the treatment of infections. In this study, we investigated an innovative, drug-free, dual-wavelength irradiation approach that combines 2 wavelengths of light, 460 nm and 405 nm, against methicillin-resistant Staphylococcus aureus (MRSA). MRSA was initially irradiated with 460-nm light (90-360 J/cm2) and subsequently irradiated with aliquots of 405-nm light (54-324 J/cm2). For in vivo studies, mouse skin was abraded and infected with approximately 107 CFUs of MRSA and incubated for 3 hours before irradiating with 460 nm (360 J/cm2) and 405 nm (342 J/cm2). Naive mouse skin was also irradiated to investigate apoptosis. We found that staphyloxanthin, the carotenoid pigment in MRSA cells, promoted resistance to the antimicrobial effects of 405-nm light. In addition, we found that the photolytic effect of 460-nm light on staphyloxanthin attenuated resistance of MRSA to 405-nm light killing. Irradiation of 460 nm alone did not elicit any antimicrobial effect on MRSA. In a proof-of-principle mouse skin abrasion infection model, we observed significant killing of MRSA using the dual-wavelength irradiation approach. However, when either wavelength of light was administered alone, no significant decrease in bacterial viability was observed. Moreover, exposure of the dual-wavelength irradiation to naive mouse skin did not result in any visible apoptosis. In conclusion, a dual-wavelength irradiation strategy may offer an innovative, effective, and safe approach for the treatment of skin infections caused by MRSA.

Highlights

  • In recent years, the threat of antimicrobial resistance has become one of the most important concerns for public health

  • We investigated whether the presence of STX within methicillin-resistant Staphylococcus aureus (MRSA) is responsible for its inherent resistance to antimicrobial blue light (aBL) (405 nm)

  • We investigated the role of STX in promoting resistance to 405-nm light killing in MRSA

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Summary

Introduction

The threat of antimicrobial resistance has become one of the most important concerns for public health. Antimicrobial blue light (aBL) at a 405-nm wavelength has been emerging as a potential alternative treatment for localized infections [5]. The accepted mechanism responsible for the antimicrobial effects of aBL (405 nm) is through excitation of endogenous photosensitizing porphyrins and the subsequent generation of singlet oxygen, resulting in lipid peroxidation, DNA damage, cell wall damage, and cellular apoptosis of microbial cells [5]. We report a potentially novel dual-wavelength irradiation approach using the combination of 460-nm and 405-nm light, which exploited the STX photolytic effect of 460-nm light to sensitize MRSA to 405-nm light

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