Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, A.N. Bach Institute of Biochemistry, Moscow, Russia.
Appl Microbiol Biotechnol. 2021 May;105(10):4099-4109. doi: 10.1007/s00253-021-11349-0. Epub 2021 May 17.
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.
抗药性多重耐药菌的传播导致了对抗这些疾病的新方法的发展。除了耐药性之外，结核病（结核分枝杆菌（Mtb））的重要病原体还能够在个体中无症状地潜伏多年，导致潜伏性结核病。在这种休眠状态下，Mtb 细胞也对已知的抗生素具有抗性。在这方面，光动力灭活（PDI）可以作为抗生素的有效替代方法，因为其作用是基于独立于特定抗生素靶标存在的情况下产生活性氧形式，从而使耐药和休眠细菌失活。在这篇综述中，我们总结了 PDI 在消除分枝杆菌属代表物方面的应用实例，包括体外和体内。根据已发表的结果，包括在 PDI 方案中使用光敏剂可显著提高致死效果。这些实验主要使用化学合成的光敏剂进行，这些光敏剂需要被运送到细菌感染区域，这限制了 PDI 在表面（皮肤）疾病中的应用。在这方面，内源性光敏剂（主要是卟啉）可用于解决运输问题。体外实验表明，使用内源性卟啉（包括 Mtb）有效应用 PDI 可消除分枝杆菌，这些物质的细胞内含量可通过 5-氨基酮戊酸（卟啉合成的前体）给药来提高。PDI 还可用于休眠分枝杆菌，其特征是内源性卟啉水平高。因此，PDI 可以有效地消除耐药分枝杆菌。现代透光技术的应用为 PDI 在临床环境中的应用开辟了新的可能性。
批判性地回顾了光动力灭活分枝杆菌的潜在影响。
描述了使用外源性和内源性光敏剂对分枝杆菌进行光灭活的方法。
讨论了光动力灭活在治疗结核病中的应用前景。
