Enhancement of 5-Aminolevulinic Acid-Mediated Photodynamic Inactivation of Proteus mirabilis Using Phosphoric and Bisaminophosphinic Acids as Permeabilizing Agents

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