Abstract
Diseases caused by multi-drug resistant pathogens have become a global concern. Therefore, new approaches suitable for treating these bacteria are urgently needed. In this study, we analyzed genetically encoded photosensitizers (PS) related to the green fluorescent protein (GFP) or light-oxygen-voltage (LOV) photoreceptors for their exogenous applicability as light-triggered antimicrobial agents. Depending on their specific photophysical properties and photochemistry, these PSs can produce different toxic ROS (reactive oxygen species) such as O2•− and H2O2 via type-I, as well as 1O2 via type-II reaction in response to light. By using cell viability assays and microfluidics, we could demonstrate differences in the intracellular and extracellular phototoxicity of the applied PS. While intracellular expression and exogenous supply of GFP-related PSs resulted in a slow inactivation of E. coli and pathogenic Gram-negative and Gram-positive bacteria, illumination of LOV-based PSs such as the singlet oxygen photosensitizing protein SOPP3 resulted in a fast and homogeneous killing of these microbes. Furthermore, our data indicate that the ROS type and yield as well as the localization of the applied PS protein can strongly influence the antibacterial spectrum and efficacy. These findings open up new opportunities for photodynamic inactivation of pathogenic bacteria.
Highlights
Since the rapid worldwide emergence of multi-drug resistant bacteria, in conjunction with a decline in the development and production of new antimicrobial agents, the efficient treatment of various life-threatening pathogens has become increasingly endangered
photodynamic therapy (PDT) and Antimicrobial photodynamic inactivation (aPDI) combine the use of visible light with a light-sensitive dye—referred to as photosensitizer (PS)—and are based on the local formation of toxic reactive oxygen species (ROS)
We demonstrated that most LOV-based fluorescent proteins, which were originally designed as alternative reporters for the in vivo analysis of oxygen-limited systems [45,46], were potent photosensitizers that could be applied for a light-controlled killing of E. coli when expressed intracellularly [47]
Summary
Since the rapid worldwide emergence of multi-drug resistant bacteria, in conjunction with a decline in the development and production of new antimicrobial agents, the efficient treatment of various life-threatening pathogens has become increasingly endangered. For this reason, major research efforts aim to develop alternative antimicrobial therapies to prevent, treat, and eliminate multidrug resistance [1,2,3]. Because of the broad spectrum of ROS-sensitive targets, aPDI does not induce resistances in microorganisms and further allows efficient inactivation of multi-drug resistant pathogens [9,10,11]
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