BioLambda, Scientific and Commercial LTD, São Paulo, SP, Brazil.; Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil..
School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
J Photochem Photobiol B. 2020 Jul;208:111893. doi: 10.1016/j.jphotobiol.2020.111893. Epub 2020 May 11.
Microbial drug-resistance demands immediate implementation of novel therapeutic strategies. Antimicrobial photodynamic therapy (aPDT) combines the administration of a photosensitizer (PS) compound with low-irradiance light to induce photochemical reactions that yield reactive oxygen species (ROS). Since ROS react with nearly all biomolecules, aPDT offers a powerful multitarget method to avoid selection of drug-resistant strains. In this study, we assayed photodynamic inactivation under a standardized method, combining methylene blue (MB) as PS and red light, against global priority pathogens. The species tested include Acinetobacter baumannii, Klebsiella aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans. Our strain collection presents resistance to all tested antimicrobials (>50). All drug-resistant strains were compared to their drug-sensitive counterparts. Regardless of resistance phenotype, MB-aPDT presented species-specific dose-response kinetics. More than 5log reduction was observed within less than 75 s of illumination for A. baumannii, E. coli, E. faecium, E. faecalis and S. aureus and within less than 7 min for K. aerogenes, K. pneumoniae, P. aeruginosa, C. albicans and C. neoformans. No signs of correlations in between drug-resistance profiles and aPDT sensitivity were observed. Therefore, MB-aPDT can provide effective therapeutic protocols for a very broad spectrum of pathogens. Hence, we believe that this study represents a very important step to bring aPDT closer to implementation into mainstream medical practices.
微生物的耐药性要求立即实施新的治疗策略。抗菌光动力疗法(aPDT)将光敏剂(PS)化合物与低强度光联合使用,以诱导产生活性氧(ROS)的光化学反应。由于 ROS 与几乎所有生物分子反应,aPDT 提供了一种强大的多靶点方法,可避免耐药菌株的选择。在这项研究中,我们按照标准化方法评估了亚甲蓝(MB)作为 PS 和红光的光动力失活作用,针对全球优先病原体。测试的物种包括鲍曼不动杆菌、产气肠杆菌、大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌、粪肠球菌、屎肠球菌、金黄色葡萄球菌、白色念珠菌和新型隐球菌。我们的菌株集合对所有测试的抗菌药物都具有耐药性(>50)。所有耐药菌株均与药敏对照株进行了比较。无论耐药表型如何,MB-aPDT 均表现出物种特异性的剂量反应动力学。在不到 75 秒的光照时间内,对鲍曼不动杆菌、大肠杆菌、粪肠球菌、屎肠球菌和金黄色葡萄球菌观察到超过 5log 的减少,而对产气肠杆菌、肺炎克雷伯菌、铜绿假单胞菌、白色念珠菌和新型隐球菌则在不到 7 分钟的时间内观察到。未观察到耐药谱和 aPDT 敏感性之间存在相关性的迹象。因此,MB-aPDT 可以为非常广泛的病原体提供有效的治疗方案。因此,我们认为这项研究是将 aPDT 更接近实施到主流医疗实践的重要一步。