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光二噻嗪对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌光动力疗法的效果:在生物膜及大蜡螟实验模型中的研究

Effects of antimicrobial photodynamic therapy with photodithazine® on methicillin-resistant Staphylococcus aureus (MRSA): Studies in biofilms and experimental model with Galleria mellonella.

作者信息

Souza Beatriz Müller N, Miñán Alejandro Guillermo, Brambilla Isabelle Ribeiro, Pinto Juliana Guerra, Garcia Maíra Terra, Junqueira Juliana Campos, Ferreira-Strixino Juliana

机构信息

Photobiology Applied to Health (PhotoBioS Lab), Universidade do Vale do Paraíba (UNIVAP), São José dos Campos, São Paulo, Brazil.

Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina.

出版信息

J Photochem Photobiol B. 2024 Mar;252:112860. doi: 10.1016/j.jphotobiol.2024.112860. Epub 2024 Feb 3.

DOI:10.1016/j.jphotobiol.2024.112860
PMID:38330692
Abstract

Staphylococcus aureus infections are a severe health problem due to the high mortality rate. Conventional treatment of these infections is via the administration of antibiotics. However, its indiscriminate use can select resistant microorganisms. Thus, it is necessary to develop alternatives for antibiotic therapy. Antimicrobial Photodynamic Therapy (aPDT), a therapeutic method that associates a photosensitizer (PS), a light source with adequate wavelength to the PS, interacts with molecular oxygen generating reactive oxygen species responsible for cell inactivation, is a viable alternative. This work aimed to analyze, in vitro and in vivo, the action of aPDT with PS Photodithazine® (PDZ) on the methicillin-resistant S. aureus (MRSA) strain. In the in vitro method, the S. aureus biofilm was incubated with PDZ at 50 and 75 μg.mL for 15 min, adopting the light dose of 25, 50, and 100 J/cm. In addition, PS interaction, formation of reactive oxygen species (ROS), bacterial metabolism, adhesion, bacterial viability, and biofilm structure were evaluated by scanning electron microscopy. Subsequently, the strain was inoculated into models of Galleria mellonella, and the survival curve, health scale, blood cell analysis, and CFU/mL of S. aureus in the hemolymph were analyzed after aPDT. In the in vitro results, bacterial reduction was observed in the different PDZ concentrations, highlighting the parameters of 75 μg.mL of PDZ and 100 J/cm. As for in vivo results, aPDT increased survival and stimulated the immune system of G. mellonella infected by S. aureus. aPDT proved effective in both models, demonstrating its potential as an alternative therapy in treating MRSA bacterial infections.

摘要

由于死亡率高,金黄色葡萄球菌感染是一个严重的健康问题。这些感染的传统治疗方法是使用抗生素。然而,抗生素的滥用会选择耐药微生物。因此,有必要开发抗生素治疗的替代方法。抗菌光动力疗法(aPDT)是一种将光敏剂(PS)、与PS波长适配的光源相结合的治疗方法,与分子氧相互作用产生活性氧,导致细胞失活,是一种可行的替代方法。这项工作旨在体外和体内分析含PS Photodithazine®(PDZ)的aPDT对耐甲氧西林金黄色葡萄球菌(MRSA)菌株的作用。在体外实验中,将金黄色葡萄球菌生物膜与50和75μg/mL的PDZ孵育15分钟,采用25、50和100 J/cm的光剂量。此外,通过扫描电子显微镜评估PS相互作用、活性氧(ROS)形成、细菌代谢、粘附、细菌活力和生物膜结构。随后,将该菌株接种到大蜡螟模型中,在aPDT后分析大蜡螟的存活曲线、健康评分、血细胞分析以及血淋巴中金黄色葡萄球菌的CFU/mL。在体外实验结果中,在不同PDZ浓度下均观察到细菌减少,突出了75μg/mL的PDZ和100 J/cm的参数。至于体内实验结果,aPDT提高了感染金黄色葡萄球菌的大蜡螟的存活率并刺激了其免疫系统。aPDT在两个模型中均被证明有效,证明了其作为治疗MRSA细菌感染的替代疗法的潜力。

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