Enhancement of\n5‑Aminolevulinic Acid-Mediated\nPhotodynamic Inactivation of Proteus mirabilis Using Phosphoric and Bisaminophosphinic Acids as Permeabilizing\nAgents

The purpose of this work was to examine the effect of\nphosphoric\nand bisaminophosphinic acids on the effectiveness of photoinactivation\nof Proteus mirabilis with 5-aminolevulinic\nacid (5-ALA) as a precursor of protoporphyrin IX. Two diode lasers\nλ = 404 nm (radiation intensity 26 mW cm<sup>–2</sup>) and λ = 630 nm (radiation intensity 55 mW cm<sup>–2</sup>) were used as sources of light. The most effective agent was (<i>R</i>)-(−)-1,1′-binaphthyl-2,2′-diylhydrogen\nphosphate, and a significant improvement in bactericidal effect of\n5-ALA-aPDI was achieved by pretreating P. mirabilis with this compound at nontoxic concentrations of 0.368 mM. It was\nfound that 15 min of blue light illumination was enough to achieve\nbacterial cell mortality of 99.999%. Photoelimination of this pathogen\nusing red light was less effective, and the required killing effect\n(at least 99.99%) was not achieved until 45 min of exposure. The mechanism\nof increased pathogen destruction by the examined acids is multifaceted\nand includes not only the destabilization of the outer bacterial cell\nmembrane by organophosphates but also an increase in the level of\nprotoporphyrin IX in cells due to chelation of iron ions. Furthermore,\na synergistic effect of intracellular photosensitizers and (<i>R</i>)-(−)-1,1′-binaphthyl-2,2′-diylhydrogen\nphosphate acting as an additional blue/red light-induced photosensitizer\ncannot be excluded.