用于治疗多重耐药细菌感染的转基因噬菌体(综述)

K. Bagandova, E. Zulkarneev, I. Kiseleva, T. Mizaeva, A. Vorobev, O. G. Efimova, M. P. Medvedovskaya, M. A. Pasivkina, A. V. Aleshkin
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摘要

由于耐多药生物(mdro)的迅速传播,抗生素耐药性是一个紧迫而未解决的问题。另一种方法是医学上使用噬菌体,与广谱抗生素相比,噬菌体对特定细菌菌株具有选择性和裂解活性。噬菌体的分离是一个多步骤、繁琐和劳动密集型的技术,各种噬菌体的生理学研究还很模糊。这些缺陷阻碍了噬菌体制剂的流动生产,需要严格的质量控制。在这里,我们回顾了现有的关于转基因噬菌体的文献,特别是研究了这种噬菌体治疗多重耐药感染的功效。基因修饰噬菌体在多重耐药感染患者中显示出高效率,无论是作为主要治疗方式还是作为抗生素治疗方案的辅助治疗。转基因噬菌体的主要优势是更广泛和更高的裂解活性,因为它们可以靶向抗生素抗性基因,如外排泵,以及低免疫原性,这延迟了它们被免疫细胞消除。我们认为,转基因噬菌体能够克服天然噬菌体的缺点,可以用于预防和治疗细菌感染,特别是由mdro引起的细菌感染。
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Genetically modified bacteriophages creating for the treatment of infections caused by multidrug resistant bacteria (review)
Antibiotic resistance represents an urgent and unresolved issue due to a rapid spread of multidrug-resistance organisms (MDROs). An alternative approach is the medical use of bacteriophages which have selective and lytic activity against specific bacterial strains, in contrast to broad-spectrum antibiotics. Isolation of bacteriophages is a multi-step, tedious, and labour-intensive technique, and physiology of various bacteriophages has been vaguely studied. These drawbacks hamper the flow production of bacteriophage preparations and require a stringent quality control. Here, we review the existing literature on genetically modified bacteriophages, in particular studies which examined efficacy of such bacteriophages for the treatment of multidrug-resistant infections. Genetically modified bacteriophages showed high efficiency in patients with multidrug-resistant infections applied either as a main treatment modality or as an adjuvant therapy added to the antibiotic treatment protocols. The key advantage of genetically modified bacteriophages is broader and higher lytic activity, as they can target antibiotic resistance genes such as efflux pumps, and low immunogenicity which delays their elimination by immune cells. We propose that genetically modified bacteriophages are able to overcome the shortcomings of natural bacteriophages and can be implemented for the prevention and treatment of bacterial infections, in particular those caused by MDROs.
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