Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
Department of Microbiology and Immunology, Montana State University , Bozeman, MT, USA.
Gut Microbes. 2020 Nov 9;12(1):1-15. doi: 10.1080/19490976.2020.1851999.
is an enteric bacterial pathogen that can a cause nosocomial infection leading to debilitating colitis. The development of a murine model of infection has led to fundamental discoveries in disease pathogenesis and the host immune response to infection. Recently, endogenously present in the microbiota of mice has been reported and was found to complicate interpretation of mouse studies. Here, we report a novel strain, named NTCD-035, isolated from the microbiota of our mouse colony. The presence of NTCD-035 in mice prior to challenge with a highly pathogenic strain (VPI10463) led to significantly reduced disease severity. Phylogenetic characterization derived from whole genome sequencing and PCR ribotyping identified the isolate as a novel clade 1, ribotype 035 strain that lacks the pathogenicity locus required to produce toxins. Deficiency in toxin production along with sporulation capacity and secondary bile acid sensitivity was confirmed using assays. Inoculation of germ-free mice with NTCD-035 did not cause morbidity despite the strain readily colonizing the large intestine. Implementation of a culture-based screening procedure enabled the identification of mice harboring in their microbiota, the establishment of a -free mouse colony, and a monitoring system to prevent future contamination. Taken together, these data provide a framework for screening mice for endogenously harbored and support clinical findings that demonstrate the therapeutic potential of non-toxigenic strains in preventing associated disease. : - Pathogenicity locus, - Colony forming units, - toxin-A, - toxin-B, binary toxin A, binary toxin B, binary toxin R, non-toxigenic .
是一种肠道细菌病原体,可导致医院获得性感染,引起衰弱性结肠炎。感染的小鼠模型的发展导致了对疾病发病机制和宿主对感染的免疫反应的基本发现。最近,报道了内源性存在于小鼠微生物群中的,并且发现它使小鼠研究的解释复杂化。在这里,我们报告了一种从我们的小鼠群的微生物群中分离出的新型菌株,命名为 NTCD-035。在挑战具有高致病性菌株(VPI10463)之前,NTCD-035 存在于小鼠中会导致疾病严重程度显着降低。基于全基因组测序和 PCR 核糖体分型的系统发育特征将分离株鉴定为新型 1 群,035 型菌株,缺乏产生毒素所需的毒力基因座。通过毒素产生、孢子形成能力和次级胆汁酸敏感性测定证实了缺失毒素产生能力。尽管该菌株可轻易定植大肠,但用 NTCD-035 接种无菌小鼠不会引起发病。实施基于培养的筛选程序可识别出在其微生物群中携带的小鼠,建立无的小鼠群,并建立监测系统以防止将来的污染。总的来说,这些数据为筛选内源携带的小鼠提供了一个框架,并支持临床发现,即非产毒菌株在预防相关疾病方面具有治疗潜力。:- 毒力基因座,- 菌落形成单位,- 毒素-A,- 毒素-B,- 双功能毒素 A,- 双功能毒素 B,- 双功能毒素 R,- 非产毒。