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沙门氏菌噬菌体治疗:噬菌体治疗的新评价。

Bacteriophage therapy of Salmonella enterica: a fresh appraisal of bacteriophage therapy.

机构信息

Faculty of Biotechnology, University of Naples Federico II, Naples, Italy.

出版信息

J Infect Dis. 2010 Jan 1;201(1):52-61. doi: 10.1086/648478.

DOI:10.1086/648478
PMID:19929381
Abstract

BACKGROUND

The most serious criticisms leveled at bacteriophage therapy are as follows: phages induce neutralizing antibodies, phages are active only when administered shortly after bacterial infection, and phage-resistant bacteria emerge rapidly in the course of therapy.

METHODS

Phages lytic for several Salmonella enterica serovars were isolated by means of standard protocols from feces of patients with gastroenteritis. Growth of S. enterica serovar Paratyphi B (Salp572(phi1S)) in the presence of phage phi1 (selected from among 8 phages for its larger host range) provided a phage phi1-resistant bacterial strain (Salp572(phi1R)). The properties of the Salp572(phi1S) and Salp572(phi1R) strains and of phage phi1 were studied in a mouse model of experimental infection.

RESULTS

Phages induced nonneutralizing antibodies and were active 2 weeks after experimental infection of mice; phage-resistant bacteria were avirulent and short lived in vivo. More importantly, phage-resistant bacteria were excellent vaccines, protecting against lethal doses of heterologous S. enterica serovars.

CONCLUSIONS

Phage therapy effectiveness has not yet been properly assessed.

摘要

背景

噬菌体疗法最严重的批评如下:噬菌体诱导中和抗体,噬菌体仅在细菌感染后不久给药时才具有活性,并且在治疗过程中噬菌体耐药细菌迅速出现。

方法

通过标准方案从肠胃炎患者的粪便中分离出几种肠沙门氏菌血清型的裂解噬菌体。噬菌体 phi1(从 8 种噬菌体中选择,因其宿主范围更广)的存在促进了肠沙门氏菌血清型副伤寒 B(Salp572(phi1S))的生长,从而产生了一种噬菌体 phi1 耐药的细菌株(Salp572(phi1R))。在实验感染小鼠模型中研究了 Salp572(phi1S)和 Salp572(phi1R)菌株以及噬菌体 phi1 的特性。

结果

噬菌体诱导非中和抗体,并且在实验感染小鼠 2 周后仍具有活性;噬菌体耐药细菌在体内毒力较弱且存活时间短。更重要的是,噬菌体耐药细菌是优良的疫苗,可预防同源和异源肠沙门氏菌血清型的致死剂量感染。

结论

噬菌体疗法的有效性尚未得到适当评估。

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