Department of Microbiology, Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Paris, France.
Antimicrob Agents Chemother. 2012 Dec;56(12):6235-42. doi: 10.1128/AAC.00602-12. Epub 2012 Sep 24.
In vivo bacteriophage targeting of enteroaggregative Escherichia coli (EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. These decreases in ileal and fecal bacterial concentrations were only transient, since 55989Str concentrations returned to their original levels 3 days later. These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophages in vivo for the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.
采用 O104:H4 55989Str 株和三种毒性噬菌体混合物的小鼠肠道定植模型评估了肠聚集性大肠杆菌 (EAEC) 的体内噬菌体靶向作用。该定植模型模拟了人类无症状的肠道携带。在饮用水中添加噬菌体混合物 24 小时，以剂量依赖的方式强烈降低回肠中的 55989Str 浓度，而对粪便中的 55989Str 浓度的降低作用较弱。这些回肠和粪便细菌浓度的下降是短暂的，因为 3 天后 55989Str 浓度恢复到原来的水平。这些短暂的下降与小鼠微生物群无关，因为在无菌小鼠中也获得了类似的结果。我们研究了每种噬菌体在回肠和粪便环境中的感染性，发现小鼠回肠中的 55989Str 细菌对所有三种噬菌体均具有易感性，而粪便中的 55989Str 细菌仅对一种噬菌体具有易感性。我们的研究结果首次证明，肠道中细菌对毒性噬菌体感染的易感性并非均匀一致；这突出表明需要对体内细菌和噬菌体之间的相互作用进行详细表征，以进一步开发针对无症状人类携带者肠道中肠道病原体的噬菌体治疗。
