Detection and elimination of a novel non-toxigenic Clostridioides difficile strain from the microbiota of a mouse colony.
Detection and elimination of a novel non-toxigenic Clostridioides difficile strain from the microbiota of a mouse colony.
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DOI：
10.1080/19490976.2020.1851999
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Abt MC
中科院分区：
文献类型：
--
作者：
Maslanka JR;Gu CH;Zarin I;Denny JE;Broadaway S;Fett B;Mattei LM;Walk ST;Abt MC
艰难梭菌是一种肠道细菌病原体，可引起院内感染，导致衰弱性结肠炎。艰难梭菌感染的小鼠模型的开发导致了疾病发病机制和宿主对感染的免疫反应的基本发现。最近，有报道称，小鼠微生物群中内源性存在艰难梭菌，并且发现该菌株使小鼠研究的解释变得复杂。在这里，我们报告了一种新的艰难梭菌菌株，名为 NTCD-035，是从我们的小鼠群体的微生物群中分离出来的。在用高致病性艰难梭菌菌株（VPI10463）攻击之前，NTCD-035在小鼠体内的存在导致疾病严重程度显着降低。来自全基因组测序和 PCR 核糖分型的系统发育特征鉴定该分离株为新的进化枝 1、核糖型 035 菌株，缺乏产生毒素所需的致病性位点。使用体外测定证实了毒素产生以及孢子形成能力和次级胆汁酸敏感性的缺陷。尽管该菌株很容易在大肠中定殖，但给无菌小鼠接种 NTCD-035 并不会引起发病。实施基于培养的筛选程序能够识别微生物群中携带艰难梭菌的小鼠，建立无艰难梭菌的小鼠群体，以及防止未来污染的监测系统。总而言之，这些数据提供了筛选小鼠内源性艰难梭菌的框架，并支持临床发现，证明非产毒菌株在预防艰难梭菌相关疾病方面具有治疗潜力。缩写：PaLoc - 致病位点，CFU - 菌落形成单位，TcdA - 毒素-A，TcdB - 毒素-B，CdtA - 二元毒素 A，CdtB - 二元毒素 B，CdtR - 二元毒素 R，NTCD - 非产毒艰难梭菌
Clostridioides difficile is an enteric bacterial pathogen that can a cause nosocomial infection leading to debilitating colitis. The development of a murine model of C. difficile infection has led to fundamental discoveries in disease pathogenesis and the host immune response to infection. Recently, C. difficile endogenously present in the microbiota of mice has been reported and was found to complicate interpretation of mouse studies. Here, we report a novel C. difficile 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 C. difficile 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 in vitro 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 C. difficile in their microbiota, the establishment of a C. difficile-free mouse colony, and a monitoring system to prevent future contamination. Taken together, these data provide a framework for screening mice for endogenously harbored C. difficile and support clinical findings that demonstrate the therapeutic potential of non-toxigenic strains in preventing C. difficile associated disease. Abbreviations: PaLoc - Pathogenicity locus, CFUs - Colony forming units, TcdA - toxin-A, TcdB - toxin-B, CdtA - binary toxin A, CdtB - binary toxin B, CdtR - binary toxin R, NTCD - non-toxigenic C. difficile
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美国梭菌艰难梭菌感染和结果负担的趋势。
DOI：
10.1056/nejmoa1910215
发表时间：
2020-04-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guh AY;Mu Y;Winston LG;Johnston H;Olson D;Farley MM;Wilson LE;Holzbauer SM;Phipps EC;Dumyati GK;Beldavs ZG;Kainer MA;Karlsson M;Gerding DN;McDonald LC;Emerging Infections Program Clostridioides difficile Infection Working Group
通讯作者：
Emerging Infections Program Clostridioides difficile Infection Working Group
影响因子：
--
作者：
Bouillaut, Laurent;McBride, Shonna M;Sorg, Joseph A
通讯作者：
Sorg, Joseph A
DOI：
10.4049/jimmunol.1200821
发表时间：
2012-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hasegawa M;Kamada N;Jiao Y;Liu MZ;Núñez G;Inohara N
通讯作者：
Inohara N
影响因子：
3.3
作者：
Dingle KE;Elliott B;Robinson E;Griffiths D;Eyre DW;Stoesser N;Vaughan A;Golubchik T;Fawley WN;Wilcox MH;Peto TE;Walker AS;Riley TV;Crook DW;Didelot X
通讯作者：
Didelot X
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.