Antimicrobial photodynamic inactivation mediated by a class of dual-action light-activated antibiotics: tetracyclines is potentiated by potassium iodide (Conference Presentation)

Abstract

Antimicrobial photodynamic inactivation (aPDI) is a new approach to killing microbial cells involving the excitation of photosensitizers (PS) by the correct wavelength of light to produce microbicidal reactive oxygen species. aPDI is independent of the antibiotic resistance status of the target cells, and is thought unlikely to produce resistance itself. Among a wide range of antimicrobial PS that have so far 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. Demeclocycline (DMCT) can be efficiently activated by blue light (405 nm), while doxycycline (DOTC) is excited best by UVA light (360 nm). Both compounds were able to eradicate Gram-positive and Gram-negative bacteria at concentrations up to (100µM) and fluences up to 10J/cm2. The addition of potassium iodide (400mM) potentiates bacteria killing by up to six extra logs with little amount of DMCT and DOTC (5µM). In contrast to methylene blue (MB), tetracyclines can photoinactivate bacteria in rich growth medium. Bacteria regrowth inhibition and even further bacterial killing were observed when bacteria were partially killed with photosensitized DOTC or DMCT, while MB allowed complete regrowth. MIC studies were carried out either in the dark or exposed to continuous blue light (0.5mW/cm2). Up to 3 extra steps (8-fold) of antibiotic activity was found in the light compared to dark, while 5 extra steps (32-fold) of that was observed with 200mM KI. The mechanism is proposed to be singlet oxygen addition to iodine anion to form peroxyiodine which can decomposes into hydrogen peroxide and molecular iodine.