Photodynamic therapy: a new antimicrobial approach to infectious disease?

Abstract

Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(-) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(-) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naive strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin.

A comparative in vitro photoinactivation study of clinical isolates of multidrug-resistant pathogens

“…In the Gramnegative E. coli, the polycationic nature of the pL-ce6 conjugate gives higher binding affinity to LPS and is better at displacing the divalent cations referred to above, thus causing "selfpromoted uptake". 5,20,21 In summary, in our study, the selected MDR isolates were more susceptible to PDI-mediated killing than their ATCC reference strains. The PDI efficacies of pL-ce6 and TBO were not affected by the antibiotic resistance mechanism that presented in MRSA and ESBL-producing E. coli.…”

“…They possess a slightly negatively charged surface and are also sensitive to cationic PS, although anionic and neutral PSs can also be used to eradicate Gram-positive bacteria. 5,6,19 The susceptibility differences observed between E. coli and S. aureus and pL-ce6 and TBO may be due to their different chemical properties, as indicated by Demidova and Hamblin et al 12 Although both pL-ce6 and TBO are cationic, pL-ce6 possesses a relatively larger molecular weight and the molecule has a greater number of potentially positively charged groups than TBO. The large molecular weight of pL-ce6 may not facilitate its ready penetration into the cell wall of the Gram-positive S. aureus leading to photodestruction.…”

“…PDI employs nontoxic photosensitizers (PSs), which localize in the microbial cells and are activated by a specific wavelength of visible light. 5 The excited-state PS reacts with in situ molecular oxygen and transfers its energy to generate reactive oxygen species (ROS), such as singlet oxygen and superoxide anion. These ROS can cause damage to cell walls, proteins, nucleic acids, and membrane lipids, eventually causing cell death.6 , 7…”

Rose bengal uptake by E. faecalis and F. nucleatum and light-mediated antibacterial activity measured by flow cytometry

“…During antibacterial photodynamic therapy (aPDT), reactive oxygen derivates are produced by the interaction of visible light with a photoabsorbing chemical called a photosensitizer (PS) [1]. Photons excite the PS to the highly unstable singlet state, which then shifts to the long-lived triplet state before transferring electrons to organic molecules or energy to molecular oxygen, respectively producing free radicals (type I mechanism) or singlet oxygen ( 1 O 2 -type II mechanism) [2][3][4].…”

Photophysical properties and intracellular imaging of water-soluble porphyrin dimers for two-photon excited photodynamic therapy

“…3 PDT drugs (or photosensitisers) achieve their therapeutic effect by generating a cytotoxic species in the presence of light, by either electron-transfer (Type I) or energy-transfer (Type II) processes. The majority of 30 photosensitisers are tetrapyrroles or porphyrinoids; these drugs cause cell death by transferring energy to oxygen, producing the highly reactive singlet excited state of molecular oxygen, 1 O 2 ( 1 !…”