Optimization of Optical Parameters for Improved Photodynamic Therapy of Staphylococcus Aureus Using Endogenous Coproporphyrin III

Abstract

The increased incidence of antibiotic-resistant bacteria, like methicillin-resistant S. aureus, necessitates treatments that prevent the development of further resistance. One method that has shown promise in this regard is antimicrobial photodynamic therapy (aPDT). It has been recently shown that Gram-positive bacteria can be endogenously photosensitized by inducing the accumulation of coproporphyrin III (CPIII) through the administration of VU0038882 and δ-aminolevulinic acid hydrochloride. However, as previous attempts of endogenous aPDT of Gram-positive bacteria operated under the prior assumption that the accumulated photosensitizer was protoporphyrin IX, optimal activation of CPIII did not occur. The purpose of this study was to determine the efficacy of killing Gram-positive bacteria using coproporphyrin III-mediated aPDT. Optimal targeting of the main absorption peak of CPIII was found to improve the efficacy of treatment as compared to previously reported results. Additionally, it was found that significant reductions in bacterial viability can be obtained by targeting the minor absorption peaks of CPIII, provided that enough light is supplied. It was predicted that these different wavelengths would be required to optimally treat infections localized at different depths in the skin, with blue light working better close the surface and red light working better deep in the skin. It was also discovered that using multiple light sources of different wavelengths induces a greater reduction in the viability of S. aureus as compared to using either one alone. These results suggest that endogenous aPDT has the potential to be further developed into a valid treatment of skin infections caused by Gram-positive bacteria.