Antimicrobial photodynamic therapy (APDT) is a promising alternative to traditional antibiotics for bacterial infections, which inactivates a broad spectrum of bacteria. However, it has some disadvantages including poor water solubility and easy aggregation of hydrophobic photosensitizers (PS), and poor tissue penetration and cytotoxicity when using UV as the light source, leading to undesired photodynamic therapy efficacy. Herein, we develop a novel water-soluble natural PS (sorbicillinoids) obtained by microbial fermentation using recombinant filamentous fungus Trichoderma reesei (T. reesei). Sorbicillinoids could effectively generate singlet oxygen (¹O₂) under ultraviolet (UV) light irradiation, and ultimately display photoinactivation activity on Gram-positive bacteria, but not Gram-negative ones. Staphylococcus aureus (S. aureus) treated with sorbicillinoids and UV light displayed high levels of intracellular reactive oxygen species (ROS), notable DNA photocleavage, and compromised cell semi-permeability without overt cell membrane disruption. Moreover, the dark toxicity, phototoxicity or hemolysis activity of sorbicillinoids is negligible, showing its excellent biocompatibility. Therefore, sorbicillinoids, a type of secondary metabolite from fungus, has a promising future as a new PS for APDT using nontoxic dose of UV light irradiation.

中文翻译：

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用于革兰氏阳性细菌光动力灭活的新型水溶性光敏剂

抗菌光动力疗法（APDT）是用于细菌感染的传统抗生素的一种有前途的替代方法，可灭活各种细菌。但是，它具有一些缺点，包括水溶性差，疏水性光敏剂（PS）易于聚集，使用UV作为光源时组织渗透性和细胞毒性差，导致不希望的光动力疗法功效。在这里，我们开发了一种新型的水溶性天然PS（山梨素），它是通过使用重组丝状真菌里氏木霉（里氏木霉）进行微生物发酵而获得的。苦参碱可有效产生单线态氧（¹ O ₂）在紫外线（UV）照射下，最终显示出对革兰氏阳性细菌的光灭活活性，但对革兰氏阴性细菌却没有。金黄色葡萄球菌（金黄色葡萄球菌）经过山梨素类药物和紫外线处理后，细胞内的活性氧（ROS）水平高，DNA裂解显着，细胞半透性降低，而不会明显破坏细胞膜。而且，山梨形类化合物的暗毒性，光毒性或溶血活性可忽略不计，显示出优异的生物相容性。因此，作为真菌的次级代谢产物的类药物山梨素类药物，有望成为使用无毒剂量的紫外线照射的APDT的新型PS。