Photoinactivation of mycobacteria to combat infection diseases: current state and perspectives

Abstract

The spread of multi-drug-resistant bacterial strains causing serious infectious diseases dictates the development of new approaches to combat these diseases. In addition to drug resistance, the important causative agent of tuberculosis (Mycobacterium tuberculosis (Mtb)) is able to persist asymptomatically in individuals for many years, causing latent forms of tuberculosis. In such a dormant state, Mtb cells are also resistant to known antibiotics. In this regard, photodynamic inactivation (PDI) could be an effective alternative to antibiotics as its action is based on the generation of active forms of oxygen independently on the presence of specific antibiotic targets, thereby inactivating both drug-resistant and dormant bacteria. In this review, we summarise examples of the application of PDI for the elimination of representatives of the genus Mycobacteria, both in vitro and in vivo. According to published results, including photosensitisers in the PDI regime results in a significantly higher lethal effect. Such experiments were mainly performed using chemically synthesised photosensitisers, which need to be transported to the areas of bacterial infections, limiting PDI usage by surface (skin) diseases. In this regard, endogenous photosensitisers (mainly porphyrins) could be used to solve the problem of transportation. In vitro experiments demonstrate the effective application of PDI for mycobacteria, including Mtb, using endogenous porphyrins; the intracellular contents of these substances can be elevated by administration of 5-aminolevulenic acid, a precursor of porphyrin synthesis. Photodynamic inactivation can also be used for dormant mycobacteria, which are characterised by high levels of endogenous porphyrins. Thus, PDI can effectively eliminate drug-resistant mycobacteria. The exploitation of modern light-transmitting techniques opens new possibilities to use PDI in clinical settings. Key points•The potential effects of photodynamic inactivation of mycobacteria are critically reviewed.•Approaches to photoinactivation of mycobacteria using exogenous and endogenous photosensitisers are described.•Prospects for the use of photodynamic inactivation in the treatment of tuberculosis are discussed.

Photodynamic Antibiofilm and Antibacterial Activity of a New Gel with 5-Aminolevulinic Acid on Infected Titanium Surfaces

“…These results are in accordance with our previous studies, in which we tested the effect of ALAD-PDI on both Gram-positive and negative bacteria [20,35]. By comparison, previous literature that used different formulations of aminolevulinic acid followed by photodynamic therapy (ala-PDI) showed contradictory results, especially on Gram-negative bacteria [36,37]. It was shown that the increase in reactive oxygen species (ROS) induced by ala-PDI promotes intracellular biopolymer leakage, photocleavage on genomic DNA, cytoplasm denaturing, and envelope injury [38].…”

Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins

“…One of the most effective photosensitizers are porphyrins 4 , among which zinc complexes standout 5 – 11 . Zn–coproporphyrin is considered as a promising compound for PDT of tumors 12 .…”

Photodynamic inactivation of different pathogenic bacteria on human skin using a novel photosensitizer hydrogel

“…17 Nevertheless, there are still problems when performing PDI on skin due to the presence of some substances on the skin surface like divalent ions. [32][33][34] Moreover, the application of a photosensitizer dissolved in pure water is not only impractical but also hampers the important wetting of the bacteria with the photosensitizer solution. Such wetting is important for the maximum proximity of photosensitizers and bacteria, which ensures good accessibility of the bacteria by singlet oxygen.…”

“…Nevertheless, there are still problems when performing PDI on skin due to the presence of some substances on the skin surface like divalent ions 32–34 . Moreover, the application of a photosensitizer dissolved in pure water is not only impractical but also hampers the important wetting of the bacteria with the photosensitizer solution.…”