Photodynamic inactivation of multi‐resistant bacteria (PIB) – a new approach to treat superficial infections in the 21^st century

Abstract

SummaryThe increasing resistance of bacteria against antibiotics is one of the most important clinical challenges of the 21 st century. Within the gram-positive bacteria the methicillin-resistant Staphylococcus aureus and Enterococcus faecium represent the major obstacle to successful therapy. Apart from the development of new antibiotics it requires additional differently constituted approaches, like photodynamic inactivation in order to have further effective treatment options against bacteria available. Certain dyes, termed photosensitizers, are able to store the absorbed energy in long-lived electronic states upon light activation with appropriate wavelengths and thus make these states available for chemical activation of the immediate surroundings. The interaction with molecular oxygen, which leads to different, very reactive and thus cytotoxic oxygen species, is highlighted. In this review the application of the photodynamic inactivation of bacteria will be discussed regarding the possible indications in dermatology, like localized skin and wound infections or the reduction of nosocomial colonization with multi-resistant bacteria on the skin. The crucial advantage of the local application of photosensitizers followed by irradiation of the area of interest is the fact that independent of the resistance pattern of a bacterium a direct inactivation takes place similarly as with an antiseptic. In this review the physical-chemical and biological basics of photodynamic inactivation of bacteria (PIB) will be discussed as well as the possible dermatological indications.

Potential applications of porphyrins in photodynamic inactivation beyond the medical scope

“…In recent years, the synthesis of new compounds for PDI has grown dramatically, many of them with very good inactivation results. Several classes of PS, such as phenothiazinium dyes (methylene blue, toluidine blue O), naturally occurring PS (chlorophylls, psoralens, perylenequinonoid pigments), tetrapyrroles (porphyrins, phthalocyanines, chlorins, bacteriochlorins) and fullerenes have been successfully tested [19][20][21] (Fig. 3).…”

Antibacterial photosensitization through activation of coproporphyrinogen oxidase

“…Furthermore, this provides proof-of-concept that activation of bacterial porphyrin production through specific activation of CgoX is a viable therapeutic strategy that could be adapted to Gram-negative bacteria and other infectious diseases (6,16,47). Therefore, the development of '882-PDT has the potential to significantly expand the value of light-based therapies for the treatment of the most common causes of skin infections.…”

“…reaction, CPIII, a photoreactive molecule of demonstrated utility in treating bacterial infections (6,16,17). Photodynamic therapy (PDT) uses a photosensitizing molecule activated by a specific wavelength of light to produce reactive oxygen species that lead to cell death (6).…”

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…In rat basophilic leukemia cells it was shown that carbon-centered radicals with a long lifetime (up to 27 seconds) were produced that may have been responsible for the phototoxicity of curcumin. These findings may explain why surface binding of curcumin could suffice to kill bacteria, given that these intermediates are more likely to transgress the cell wall than the short-lived 1 O 2 or •OH [13]. A contributory mechanism to cytotoxicity is that curcumin generates radicals or become a radical itself in a physiological environment in the absence of light, especially at pH > 6.5 [94].…”

“…Although not abundantly taken up by the bacteria, the PSs accumulate extracellularly in close proximity to the cell membrane and membrane constituents. The generation of reactive intermediates in close vicinity of cell structures either causes direct oxidation of these components or allows transmembrane diffusion of reactive intermediates and corollary oxidative damage to various intracellular targets [13]. In most instances, APDT predominantly proceeds via type II processes.…”