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持续性鸡螺杆菌定植于 C57BL/6NTac 小鼠:一种新兴人畜共患病的新型小鼠模型。

Persistent Helicobacter pullorum colonization in C57BL/6NTac mice: a new mouse model for an emerging zoonosis.

机构信息

Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.

Taconic Inc., Hudson, NY 12534, USA.

出版信息

J Med Microbiol. 2012 May;61(Pt 5):720-728. doi: 10.1099/jmm.0.040055-0. Epub 2012 Feb 2.

Abstract

Helicobacter pullorum, an enterohepatic Helicobacter species, is associated with gastroenteritis and hepatobiliary disease in humans and chickens. Recently, a novel H. pullorum outbreak in barrier-maintained rats and mice was described. In this study, persistence of infection and serological responses were further evaluated in H. pullorum-infected female C57BL/6NTac and C3H/HeNTac mice obtained from the barrier outbreak. C57BL/6NTac mice (n=36) aged 10-58 weeks were confirmed to be chronically infected with H. pullorum by PCR or culture of caecum, colon and faeces, with no evidence of hepatic infection; two of three C3H/HeNTac mice cleared H. pullorum infection by 26 weeks of age. A quantitative PCR (qPCR) assay based on the cdtB gene specific to H. pullorum demonstrated that colonization was high in the caecum and colon at 10(4)-10(6) c.f.u. equivalents per µg host DNA, and decreased by several logs from 32 to 58 weeks of age. Infected mice were seropositive by ELISA, and H. pullorum-specific IgG levels decreased as colonization was lost over time in selected mice. Consistent with the lack of pathology associated with chronic infection of C57BL/6 mice with other murine enteric helicobacters, C57BL/6NTac and C3H/HeNTac mice infected with H. pullorum did not develop gross or histological lesions of the liver or gastrointestinal tract. The cdtB-based qPCR assay can be used in screening animals, food sources and environmental samples for H. pullorum, as this food-borne pathogen has zoonotic potential. These findings will also allow future studies in murine models to dissect potential pathogenic mechanisms for this emerging pathogen.

摘要

鸡源性弯曲杆菌(Helicobacter pullorum)是一种肠-肝型弯曲杆菌,与人类和鸡的胃肠炎和肝胆疾病有关。最近,有研究报道了一种新型的鸡源性弯曲杆菌在屏障饲养的大鼠和小鼠中的爆发。在本研究中,进一步评估了从该屏障爆发中获得的感染鸡源性弯曲杆菌的雌性 C57BL/6NTac 和 C3H/HeNTac 小鼠的感染持续性和血清学反应。36 只 10-58 周龄的 C57BL/6NTac 小鼠通过 PCR 或盲肠、结肠和粪便培养确认为慢性感染鸡源性弯曲杆菌,没有肝感染的证据;3 只 C3H/HeNTac 小鼠中有 2 只在 26 周龄时清除了鸡源性弯曲杆菌感染。基于特异性针对鸡源性弯曲杆菌的 cdtB 基因的定量 PCR(qPCR)检测表明,盲肠和结肠中的定植量在 10(4)-10(6)cfu 等价物/µg 宿主 DNA 之间很高,并在 32-58 周龄时减少了几个对数级。感染小鼠通过 ELISA 呈血清阳性,并且在选定的小鼠中随着定植的丢失,鸡源性弯曲杆菌特异性 IgG 水平逐渐降低。与其他与 C57BL/6 小鼠慢性感染相关的肠型弯曲杆菌缺乏病理学相一致的是,感染鸡源性弯曲杆菌的 C57BL/6NTac 和 C3H/HeNTac 小鼠没有发展出肝脏或胃肠道的大体或组织学病变。基于 cdtB 的 qPCR 检测可用于筛查动物、食物来源和环境样本中的鸡源性弯曲杆菌,因为这种食源性病原体具有人畜共患的潜力。这些发现还将允许在未来的小鼠模型中研究该新兴病原体的潜在致病机制。

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