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硅酞菁(Pc)4的光动力抗菌作用

The photodynamic antibacterial effects of silicon phthalocyanine (Pc) 4.

作者信息

Dimaano Matthew L, Rozario Chantal, Nerandzic Michelle M, Donskey Curtis J, Lam Minh, Baron Elma D

机构信息

Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA.

Research Service, Geriatric Research Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.

出版信息

Int J Mol Sci. 2015 Apr 8;16(4):7851-60. doi: 10.3390/ijms16047851.

Abstract

The emergence of antibiotic-resistant strains in facultative anaerobic Gram-positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), is a global health issue. Typically, MRSA strains are found associated with institutions like hospitals but recent data suggest that they are becoming more prevalent in community-acquired infections. It is thought that the incidence and prevalence of bacterial infections will continue to increase as (a) more frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b) increased number of invasive medical procedures; and (c) higher incidence of neutropenia and HIV infections. Therefore, more optimal treatments, such as photodynamic therapy (PDT), are warranted. PDT requires the interaction of light, a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In this study, we investigated the efficacy and characterized the mechanism of cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine (Pc) 4 on (a) methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25923); (b) community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) (ATCC 43300); and (c) hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) (PFGE type 300). Our data include confocal image analysis, which confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell recovery assay, which showed that concentrations as low as 1.0 μM Pc 4 incubated for 3 h at 37 °C followed by light at 2.0 J/cm2 can reduce cell survival by 2-5 logs. These results are encouraging, but before PDT can be utilized as an alternative treatment for eradicating resistant strains, we must first characterize the mechanism of cell death that Pc 4-based PDT employs in eliminating these pathogens.

摘要

兼性厌氧革兰氏阳性球菌中抗生素耐药菌株的出现,如耐甲氧西林金黄色葡萄球菌(MRSA),是一个全球性的健康问题。通常,MRSA菌株与医院等机构有关,但最近的数据表明,它们在社区获得性感染中越来越普遍。据认为,细菌感染的发病率和患病率将继续上升,原因如下:(a)广谱抗生素和免疫抑制药物的使用更加频繁;(b)侵入性医疗程序的数量增加;(c)中性粒细胞减少症和HIV感染的发病率更高。因此,需要更优化的治疗方法,如光动力疗法(PDT)。PDT需要光、光敏剂和分子氧相互作用以诱导细胞毒性作用。在本研究中,我们研究了由硅酞菁(Pc)4敏化的光动力疗法对以下菌株的疗效并表征了其细胞毒性机制:(a)甲氧西林敏感金黄色葡萄球菌(MSSA)(ATCC 25923);(b)社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)(ATCC 43300);(c)医院获得性耐甲氧西林金黄色葡萄球菌(HA-MRSA)(PFGE 300型)。我们的数据包括共聚焦图像分析,其证实所有金黄色葡萄球菌菌株均摄取了Pc 4,以及活细胞回收率测定,其表明在37℃下孵育3小时,随后以2.0 J/cm2的光照处理,低至1.0 μM的Pc 4浓度可使细胞存活率降低2至5个对数。这些结果令人鼓舞,但在PDT可被用作根除耐药菌株的替代治疗方法之前,我们必须首先表征基于Pc 4的PDT在消除这些病原体时所采用的细胞死亡机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/4425053/68e6034e592c/ijms-16-07851-g001.jpg

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