Novel Water-Soluble Photosensitizer for Photodynamic Inactivation of Gram-Positive Bacteria Using Nontoxic Dose of UV Light

Abstract

Background Antimicrobial photodynamic therapy (APDT) is a promising alternative to traditional antibiotics for bacterial infections, which inactivates a broad spectrum of bacteria. However, it has some disadvantages including poor water solubility and easy aggregation of hydrophobic photosensitizers (PS), and poor tissue penetration and cytotoxicity when using UV as the light source, leading to undesired photodynamic therapy efficacy.Results In this study, we develop a novel water-soluble natural PS (sorbicillinoids) obtained by microbial fermentation using recombinant filamentous fungus Trichoderma reesei (T. reesei). Sorbicillinoids could effectively generate singlet oxygen (1O2) under ultraviolet (UV) light irradiation, and ultimately display photoinactivation activity on Gram-positive bacteria, but not Gram-negative ones. Staphylococcus aureus (S. aureus) treated with sorbicillinoids and UV light displayed high levels of intracellular reactive oxygen species (ROS), notable DNA photocleavage, and compromised cell semi-permeability without overt cell membrane disruption. Moreover, the dark toxicity, phototoxicity or hemolysis activity of sorbicillinoids is negligible, showing its excellent biocompatibility.Conclusion Sorbicillinoids obtained from T. reesei display photoinactivation activity on Gram-positive bacteria using nontoxic dose of UV light irradiation and have an excellent biocompatibility Therefore, sorbicillinoids, a type of secondary metabolite from fungus, has a promising future as a new PS for APDT.