Efficacy of Bacteriophage Therapy against Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice
Efficacy of Bacteriophage Therapy against Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice
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DOI：
10.1128/aac.00635-06
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发表时间：
2006-11
影响因子：
4.9
通讯作者：
R. Watanabe;Tetsuya Matsumoto;G. Sano;Y. Ishii;K. Tateda;Y. Sumiyama;Jumpei Uchiyama;Shingo Sakurai;S. Matsuzaki;S. Imai;K. Yamaguchi
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作者：
R. Watanabe;Tetsuya Matsumoto;G. Sano;Y. Ishii;K. Tateda;Y. Sumiyama;Jumpei Uchiyama;Shingo Sakurai;S. Matsuzaki;S. Imai;K. Yamaguchi
摘要我们通过使用与人类败血症的临床病理生理学非常相似的铜绿假单胞菌引起的肠源性败血症的小鼠模型来评估噬菌体（噬菌体）治疗的功效。口服新分离的裂解性噬菌体菌株（KPP 10）显著保护小鼠免于死亡（存活率，噬菌体处理组为66.7%，盐水处理对照组为0%; P < 0.01）。用噬菌体处理的小鼠在其血液、肝脏和脾脏中也具有较低数量的活铜绿假单胞菌细胞。与未经噬菌体处理的小鼠相比，经噬菌体处理的小鼠血液和肝脏中的炎性细胞因子（肿瘤坏死因子α TNF-α、白细胞介素-1 β [IL-1β]和IL-6）水平显著降低。噬菌体处理的小鼠胃肠道粪便中存活的铜绿假单胞菌细胞数量显着低于盐水处理的对照小鼠。我们还研究了噬菌体治疗铜绿假单胞菌引起的腹腔感染的功效，发现噬菌体治疗显著提高了小鼠的存活率，但仅在有限的实验条件下。总之，我们的研究结果表明，口服噬菌体可能对铜绿假单胞菌引起的肠源性脓毒症有效。
ABSTRACT We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group; P < 0.01). Mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-α, interleukin-1β [IL-1β], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa.