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针对ESKAPE病原体的光动力疗法:一种对抗抗菌药物耐药性(AMR)的新兴方法。

Photodynamic therapy for ESKAPE pathogens: An emerging approach to combat antimicrobial resistance (AMR).

作者信息

Mathur Akansha, Parihar Ajayraj Singh, Modi Simran, Kalra Aakanksha

机构信息

Dr. B. Lal Institute of Biotechnology, Jaipur, India.

Dr. B. Lal Institute of Biotechnology, Jaipur, India.

出版信息

Microb Pathog. 2023 Oct;183:106307. doi: 10.1016/j.micpath.2023.106307. Epub 2023 Aug 19.

Abstract

The increase in antimicrobial resistance, particularly in ESKAPE pathogens, has resulted in the dire need for new therapeutic approaches. ESKAPE is an acronym for a group of bacteria that are responsible for a majority of nosocomial and community acquired infections. The acronym stands for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These pathogens are known for their ability to develop resistance to multiple antibiotics, making them difficult to treat thus posing a significant threat to public health. In light of the alarming consequences of antimicrobial resistance, it has been estimated that, in the absence of a substantial increase in the rate of development of new effective drugs, the number of casualties related to these infections will increase from about 700,000 in 2016 up to nearly 10,000,000 in 2050 [1]. One potential strategy to treat these pathogens is photodynamic therapy (PDT). In the early 20th century, Oscar Raab observed the phototoxicity of acridine red against Paramecium caudatum, while Tappenier and Jesionek demonstrated the photodynamic effects of eosin for treating cutaneous diseases. These discoveries laid the foundation for Photodynamic Therapy (PDT), which utilizes a non-toxic photosensitizer (PS) followed by targeted light irradiation for treatment [2]. PDT involves the use of a photosensitizer, a light source, and oxygen to eliminate highly active infectious pathogens such as bacteria, viruses, and fungi. PDT is known to possess several advantages including localized treatment and fewer side effects. Various photosensitizers and light sources have been assessed in different strains, showing promising results suggesting PDT to be a promising potential treatment option. PDT utilizes PS compounds with suitable light absorption that showcase effective results against the pathogens in vitro and in vivo, including BODIPY derivatives, Methylene Blue, and other dyes like porphyrin derivatives, phthalocyanines, indole derivatives, Photophrin, etc., inhibiting the growth of infections, for both in planktonic cells and in biofilms. Combination of PDT with other therapies like efflux pump inhibitors or quorum sensing inhibitors has also proven to be efficacious. However, this domain further needs to be assessed before it reaches the society.

摘要

抗菌耐药性的增加,尤其是在ESKAPE病原体中,导致了对新治疗方法的迫切需求。ESKAPE是一组细菌的首字母缩写,这些细菌是大多数医院获得性感染和社区获得性感染的病原体。该首字母缩写代表粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属。这些病原体以其对多种抗生素产生耐药性的能力而闻名,使其难以治疗,从而对公众健康构成重大威胁。鉴于抗菌耐药性的惊人后果,据估计,在新有效药物开发速度没有大幅提高的情况下,与这些感染相关的死亡人数将从2016年的约70万增加到2050年的近1000万[1]。治疗这些病原体的一种潜在策略是光动力疗法(PDT)。在20世纪初,奥斯卡·拉布观察到吖啶红对尾草履虫的光毒性,而塔彭尼尔和耶西奥内克证明了曙红治疗皮肤病的光动力效应。这些发现为光动力疗法(PDT)奠定了基础,该疗法利用无毒的光敏剂(PS),然后进行靶向光照射进行治疗[2]。PDT涉及使用光敏剂、光源和氧气来消除高度活跃的传染性病原体,如细菌、病毒和真菌。已知PDT具有多种优点,包括局部治疗和较少的副作用。已经在不同菌株中评估了各种光敏剂和光源,显示出有希望的结果,表明PDT是一种有前途的潜在治疗选择。PDT利用具有合适光吸收的PS化合物,在体外和体内对病原体都显示出有效的结果,包括BODIPY衍生物、亚甲蓝以及其他染料,如卟啉衍生物、酞菁、吲哚衍生物、光卟啉等,抑制浮游细胞和生物膜中感染的生长。PDT与其他疗法如外排泵抑制剂或群体感应抑制剂联合使用也已证明是有效的。然而,在该领域应用于社会之前还需要进一步评估。

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