Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin

Abstract

It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or fungi. However, the aPDI activity of PF against Gram-negative bacteria is accepted to be extremely low. Here we report that the nontoxic inorganic salt potassium iodide (KI) at a concentration of 100 mM when added to microbial cells (108/mL) + PF (10 μM hematoporphyrin equivalent) + 415 nm light (10 J/cm2) can eradicate (>6 log killing) five different Gram-negative species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii), whereas no killing was obtained without KI. The mechanism of action appears to be the generation of microbicidal molecular iodine (I2/I3−) as shown by comparable bacterial killing when cells were added to the mixture after completion of illumination and light-dependent generation of iodine as detected by the formation of the starch complex. Gram-positive methicillin-resistant Staphylococcus aureus is much more sensitive to aPDI (200–500 nM PF), and in this case potentiation by KI may be mediated mainly by short-lived iodine reactive species. The fungal yeast Candida albicans displayed intermediate sensitivity to PF-aPDI, and killing was also potentiated by KI. The reaction mechanism occurs via singlet oxygen (1O2). KI quenched 1O2 luminescence (1270 nm) at a rate constant of 9.2 × 105 M−1 s−1. Oxygen consumption was increased when PF was illuminated in the presence of KI. Hydrogen peroxide but not superoxide was generated from illuminated PF in the presence of KI. Sodium azide completely inhibited the killing of E. coli with PF/blue light + KI.

Potassium iodide potentiates antimicrobial photodynamic inactivation mediated by Rose Bengal: in vitro and in vivo studies

“…Next, we confirmed the generation of hydrogen peroxide using the Amplex red assay (Fig. 4B), as we had previously observed that H 2 O 2 was generated by Photofrin and KI excited by blue light (19). We reasoned that there were two possible routes by which hydrogen peroxide could be formed.…”

“…Here the mechanism was via a mixture of a one-electron oxidation of iodide anion to form molecular iodine and a two-electron oxidation of iodide anion to form hypoiodite. It was not until we discovered (19) that aPDI mediated by the porphyrin PS known as Photofrin was also able to be strongly potentiated by KI (provided the concentration of iodide was at least 25 mM and, preferably, 100 mM) that we realized singlet oxygen was likely to be involved in the process (19,32). We were able to show not only that activation of SOSG was quenched by KI but also that the luminescence signal of singlet oxygen was quenched by iodide and that oxygen was consumed in irradiated samples containing RB and KI.…”

“…Addition of a simple KI solution to a mixture of microbial cells and many different PS (phenothiazinium dyes [15,16], titanium dioxide photocatalysis [17], and fullerenes [18]) that are subsequently excited by light can give many log units of additional killing (up to 6 logs of extra killing). We recently showed (19) that addition of KI to the traditional anticancer, porphyrin-based PS called Photofrin (PF; porfimer sodium) allowed broad-spectrum aPDI, including the eradication of Gram-negative bacteria that were previously thought to be resistant to PF photodynamic therapy (PDT) (17). In the present study, we asked the question whether the aPDI effects of the anionic dye RB would also be potentiated by addition of KI.…”

Potentiation of antimicrobial photodynamic inactivation by inorganic salts

“…We looked at a clinically approved photosensitizer called Photofrin (PF, Lerdele Pharmaceuticals Inc., Carolina, Puerto Rico) [23] (Figure 2(d)). PF is a water-soluble derivative of hematoporphyrin that was the first compound to gain worldwide regulatory approval to treat different kinds of cancer with PDT after intravenous injection [5].…”

“…Since we had found in the study using TiO 2 photocatalysis [23] that concentrations of KI of 100 mM were much better than concentrations of 10 mM, we used higher KI concentrations than we did with MB [22]. We used blue light to activate PF due to the much higher absorption coefficient at the Soret band compared to the Q-bands (200,000 compared to 3000–15,000).…”