Abstract
Antimicrobial photodynamic inactivation (aPDI) employs photosensitizing dyes activated by visible light to produce reactive oxygen species. aPDI is independent of the antibiotic resistance status of the target cells, and is thought unlikely to produce resistance itself. Among many PS that have been investigated, tetracyclines occupy a unique niche. They are potentially dual-action compounds that can both kill bacteria under illumination, and prevent bacterial regrowth by inhibiting ribosomes. Tetracycline antibiotics are regarded as bacteriostatic rather than bactericidal. Doxycycline (DOTC) is excited best by UVA light (365 nm) while demeclocycline (DMCT) can be efficiently activated by blue light (415 nm) as well as UVA. Both compounds were able to eradicate Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria (>6 log(10) steps of killing) at concentrations (10–50μM) and fluences (10-20J/cm2). In contrast to methylene blue, MB plus red light, tetracyclines photoinactivated bacteria in rich growth medium. When ~3 logs of bacteria were killed with DMCT/DOTC+light and the surviving cells were added to growth medium, further bacterial killing was observed, while the same experiment with MB allowed complete regrowth. MIC studies were carried out either in the dark or exposed to 0.5mW/cm2 blue light. Up to three extra steps (8-fold) increased antibiotic activity was found with light compared to dark, with MRSA and tetracycline-resistant strains of E. coli. Tetracyclines can accumulate in bacterial ribosomes, where they could be photoactivated with blue/UVA light producing microbial killing via ROS generation.
Highlights
The alarming rise in antibiotic resistance has led to widespread predictions of the “end of the antibiotic era” [1]
In order to assess the photostablitity of TCs, absorption spectra of DMCT and DOTC were measured before and after exposure to both BL (50 J/cm2) and UVA (50 J/cm2)
While all TCs are efficiently excited by UVA light, DMCT would be able to be efficiently excited by BL
Summary
The alarming rise in antibiotic resistance has led to widespread predictions of the “end of the antibiotic era” [1]. The O’Neill report [2] predicted that by 2050 (if nothing were done to stem the growth of multi-drug resistant bacteria) there would have been 300 million premature deaths that would have cost the world economy $100 trillion. PDT is based upon the scientific principle that many dyes absorb light and can interact with ambient oxygen to produce hydroxyl radicals (HO) or singlet oxygen (1O2). These reactive oxygen species (ROS) can kill microbial cells by causing oxidative damage to their constituent biomolecules
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