T-even-related bacteriophages as candidates for treatment of Escherichia coli urinary tract infections

T-even-related bacteriophages as candidates for treatment of Escherichia coli urinary tract infections
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DOI:
10.1007/s00705-007-0031-4
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发表时间:
2008-01
影响因子:
2.7
通讯作者:
H. Nishikawa;M. Yasuda;Jumpei Uchiyama;M. Rashel;Y. Maeda;Iyo Takemura;S. Sugihara;Takako Ujihara-Takako-Ujih
H. Nishikawa;M. Yasuda;Jumpei Uchiyama;M. Rashel;Y. Maeda;Iyo Takemura;S. Sugihara;Takako Ujihara-Takako-Ujih
中科院分区:
医学4区
文献类型:
--
作者:
H. Nishikawa;M. Yasuda;Jumpei Uchiyama;M. Rashel;Y. Maeda;Iyo Takemura;S. Sugihara;Takako Ujihara-Takako-Ujih

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多重耐药尿路病原性大肠杆菌(UPEC)在全球范围内逐渐增加。因此,我们研究了噬菌体(噬菌体)治疗UPEC菌株引起的尿路感染(UTIs)作为化疗的替代方案的可能性。除了众所周知的T4噬菌体之外,新分离的KEP 10被用作治疗性噬菌体候选物。KEP 10对UPEC菌株的溶菌谱(67%)比T4(14%)更宽。形态学和遗传学分析表明,KEP 10类似于噬菌体T4。将噬菌体T4和KEP 10注射到小鼠腹腔中,立即分布到检查的所有器官,并保持高滴度至少24 h。在37°C下,它们在小鼠和人的尿液中稳定24小时。将这些抗生素注入腹膜腔可显著降低经尿道接种UPEC菌株的小鼠的死亡率,而大多数对照小鼠在细菌感染后几天内死亡。单独用噬菌体接种不产生归因于噬菌体本身的不良作用。本研究通过实验证实了噬菌体对大肠杆菌的治疗潜力。大肠杆菌诱导的UTI和T-偶相关的UTI可能是治疗它们的合适候选物。
Multidrug-resistant uropathogenicEscherichia coli(UPEC) is increasing gradually on a worldwide scale. We therefore examined the possibility of bacteriophage (phage) therapy for urinary tract infections (UTIs) caused by the UPEC strains as an alternative to chemotherapy. In addition to the well-known T4 phage, KEP10, which was newly isolated, was used as a therapeutic phage candidate. KEP10 showed a broader bacteriolytic spectrum (67%) for UPEC strains than T4 (14%). Morphological and genetic analyses showed that KEP10 resembles phage T4. Phages T4 and KEP10 injected into the peritoneal cavity of mice were distributed immediately to all organs examined and maintained a high titer for at least 24 h. They were stable in the urine of both mice and humans for 24 h at 37°C. Administration of these phages into the peritoneal cavity caused a marked decrease in the mortality of mice inoculated transurethrally with a UPEC strain, whereas most of the control mice died within a few days of bacterial infection. Inoculation with phage alone produced no adverse effects attributable to the phage per se. The present study experimentally demonstrated the therapeutic potential of phage forE. coli-induced UTIs, and T-even-related phages may be suitable candidates with which to treat them.