Rose Bengal diacetate-mediated antimicrobial photodynamic inactivation: potentiation by potassium iodide and acceleration of wound healing in MRSA-infected diabetic mice.

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue.

In Vivo Potentiation of Antimicrobial Photodynamic Therapy in a Mouse Model of Fungal Infection by Addition of Potassium Iodide.

Antimicrobial photodynamic inactivation (aPDI) involves the use of a nontoxic dye or photosensitizer excited with visible light to produce reactive oxygen species that can kill all classes of microorganisms. Antimicrobial photodynamic therapy (aPDT) can be used in vivo as an alternative therapeutic strategy to treat localized infections due to its ability to selectively kill microbes while preserving host mammalian cells. aPDI can be potentiated by the addition of the nontoxic inorganic salt potassium iodide (KI). KI is an approved drug for antifungal therapy. The mechanism of potentiation with iodide is likely to be singlet oxygen addition to iodide to form iodine radicals, hydrogen peroxide, and molecular iodine. A previous chapter in this volume described potentiation of aPDI in vitro by addition of KI, while in this chapter we address the ability of KI to potentiate aPDT in vivo using an animal model of localized fungal infection. We employed oral candidiasis in immunosuppressed mice caused by a bioluminescent strain of Candida albicans and monitored by bioluminescence imaging.

Can light-based approaches overcome antimicrobial resistance?

The relentless rise of antibiotic resistance is considered one of the most serious problems facing mankind. This mini-review will cover three cutting-edge approaches that use light-based techniques to kill antibiotic-resistant microbial species, and treat localized infections. First, we will discuss antimicrobial photodynamic inactivation using rationally designed photosensitizes combined with visible light, with the added possibility of strong potentiation by inorganic salts such as potassium iodide. Second, the use of blue and violet light alone that activates endogenous photoactive porphyrins within the microbial cells. Third, it is used for "safe UVC" at wavelengths between 200 nm and 230 nm that can kill microbial cells without damaging host mammalian cells. We have gained evidence that all these approaches can kill multidrug resistant bacteria in vitro, and they do not induce themselves any resistance, and moreover can treat animal models of localized infections caused by resistant species that can be monitored by noninvasive bioluminescence imaging. Light-based antimicrobial approaches are becoming a growing translational part of anti-infective treatments in the current age of resistance.

Comparison of two functionalized fullerenes for antimicrobial photodynamic inactivation: Potentiation by potassium iodide and photochemical mechanisms.

A new fullerene (BB4-PPBA) functionalized with a tertiary amine and carboxylic acid was prepared and compared with BB4 (cationic quaternary group) for antimicrobial photodynamic inactivation (aPDI). BB4 was highly active against Gram-positive methicillin resistant Staphylococcus aureus (MRSA) and BB4-PPBA was moderately active when activated by blue light. Neither compound showed much activity against Gram-negative Escherichia coli or fungus Candida albicans. Therefore, we examined potentiation by addition of potassium iodide. Both compounds were highly potentiated by KI (1-6 extra logs of killing). BB4-PPBA was potentiated more than BB4 against MRSA and E. coli, while for C. albicans the reverse was the case. Addition of azide potentiated aPDI mediated by BB4 against MRSA, but abolished the potentiation caused by KI with both compounds. The killing ability after light decayed after 24 h in the case of BB4, implying a contribution from hypoiodite as well as free iodine. Tyrosine was readily iodinated with BB4-PPBA plus KI, but less so with BB4. We conclude that the photochemical mechanisms of these two fullerenes are different. BB4-PPBA is more Type 2 (singlet oxygen) while BB4 is more Type 1 (electron transfer). There is also a possibility of direct bacterial killing by electron transfer, but this will require more study to prove.