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噬菌体疗法——限制与可能。

Phage therapy--constraints and possibilities.

机构信息

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , SE-106 91 Stockholm , Sweden.

出版信息

Ups J Med Sci. 2014 May;119(2):192-8. doi: 10.3109/03009734.2014.902878. Epub 2014 Mar 30.

Abstract

The rise of antibiotic-resistant bacterial strains, causing intractable infections, has resulted in an increased interest in phage therapy. Phage therapy preceded antibiotic treatment against bacterial infections and involves the use of bacteriophages, bacterial viruses, to fight bacteria. Virulent phages are abundant and have proven to be very effective in vitro, where they in most cases lyse any bacteria within the hour. Clinical trials on animals and humans show promising results but also that the treatments are not completely effective. This is partly due to the studies being carried out with few phages, and with limited experimental groups, but also the fact that phage therapy has limitations in vivo. Phages are large compared with small antibiotic molecules, and each phage can only infect one or a few bacterial strains. A very large number of different phages are needed to treat infections as these are caused by genetically different strains of bacteria. Phages are effective only if enough of them can reach the bacteria and increase in number in situ. Taken together, this entails high demands on resources for the construction of phage libraries and the testing of individual phages. The effectiveness and host range must be characterized, and immunological risks must be assessed for every single phage.

摘要

抗生素耐药菌株的出现导致了难以治疗的感染,这使得人们对噬菌体疗法产生了浓厚的兴趣。噬菌体疗法早于抗生素治疗细菌感染,涉及使用噬菌体,即细菌病毒来对抗细菌。毒性噬菌体数量丰富,在体外已被证明非常有效,它们在大多数情况下可以在一小时内裂解任何细菌。动物和人类的临床试验显示出有希望的结果,但也表明这些治疗并非完全有效。这部分是由于研究中使用的噬菌体数量较少,实验组有限,但也因为噬菌体疗法在体内存在局限性。噬菌体与小的抗生素分子相比体积较大,并且每种噬菌体只能感染一种或几种细菌菌株。需要大量不同的噬菌体来治疗感染,因为这些感染是由遗传上不同的细菌菌株引起的。只有当足够数量的噬菌体能够到达细菌并在原位增加数量时,噬菌体才会有效。总的来说,这需要大量的资源来构建噬菌体文库和测试单个噬菌体。必须对每种噬菌体的有效性和宿主范围进行特征描述,并评估免疫风险。

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