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Photodynamic inactivation of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with Ru(Ⅱ)-based type Ⅰ/type Ⅱ photosensitizers

机译:Ru(Ⅱ)型Ⅰ/Ⅱ型光敏剂对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌的光动力学灭活作用

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Background: The introduction of new disinfection and sterilization methods, such as antimicrobial photodynamic therapy, is urgently needed for the healthcare industry, in particular to address the pervasive problem of antibiotic resistance. This study evaluated the efficacy and the mechanisms of photodynamic antimicrobial chemotherapy (PACT), also known as photodynamic inactivation (PDI) of microorganisms, induced by novel Ru(Ⅱ)-based photosensitizers against Staphylococcus aureus and methicillin-resistant S. aureus strains. Methods: The photodynamic antibacterial effects of a new class of Ru(Ⅱ)-based photosensitizers (TLD1411 and TLD1433) were evaluated against a strain of S. aureus (ATCC 25923) and a methicillin-resistant strain of S. aureus (MRSA, ATCC 33592). Bacterial samples were dosed with a range of photosensitizer concentrations (0.3-12μM) and exposed to 530nm light (90Jcm~(-2)) in normoxic conditions (ambient atmosphere) and in hypoxic conditions (0.5% O_2). Results: Both photosensitizers exerted photodynamic inactivation (PDI) of the microorganisms in normoxia, and this activity was observed in the nanomolar regime. TLD1411 and TLD1433 maintained this PDI potency under hypoxic conditions, with TLD1433 becoming even more active in the low-oxygen environment. Conclusion: The observation of activity in hypoxia suggests that there exists an oxygen-independent, Type I photoprocess for this new class of compounds in addition to the typical Type II pathway mediated by singlet oxygen. The intrinsic positive charge of the Ru(Ⅱ) metal combined with the oxygen independent activity demonstrated by this class of photosensitizers presents a new strategy for eradicating both gram-positive and gram-negative bacteria regardless of oxygenation level.
机译:背景:医疗行业迫切需要引入新的消毒和灭菌方法,例如抗微生物光动力疗法,尤其是要解决普遍存在的抗生素耐药性问题。本研究评估了新型基于Ru(Ⅱ)的光敏剂对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌菌株诱导的光动力抗菌化学疗法(PACT)(也称为微生物的光动力灭活(PDI))的功效和机理。方法:评估了新型基于Ru(Ⅱ)的光敏剂(TLD1411和TLD1433)对金黄色葡萄球菌(ATCC 25923)和耐甲氧西林金黄色葡萄球菌(MRSA,ATCC)的光动力抗菌作用。 33592)。在常氧条件下(环境气氛)和低氧条件下(0.5%O_2),向细菌样品添加一定范围的光敏剂浓度(0.3-12μM),并暴露于530nm的光(90Jcm〜(-2))中。结果:两种光敏剂均在常氧状态下对微生物产生光动力灭活(PDI),并且在纳摩尔模式下观察到了这种活性。 TLD1411和TLD1433在低氧条件下保持了这种PDI效力,而TLD1433在低氧环境中变得更加活跃。结论:在低氧状态下的活性观察表明,除了由单线态氧介导的典型II型途径外,对于这类新化合物还存在不依赖氧的I型光过程。这类光敏剂显示出Ru(Ⅱ)金属的固有正电荷与氧独立活性相结合,为消除革兰氏阳性菌和革兰氏阴性菌提供了一种新的策略,无论其氧合水平如何。

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