Sequence-based discovery of Bradyrhizobium enterica in cord colitis syndrome.
Sequence-based discovery of Bradyrhizobium enterica in cord colitis syndrome.
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DOI：
10.1056/nejmoa1211115
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发表时间：
2013-08-08
期刊：
影响因子：
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通讯作者：
Meyerson M
中科院分区：
文献类型：
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作者：
Bhatt AS;Freeman SS;Herrera AF;Pedamallu CS;Gevers D;Duke F;Jung J;Michaud M;Walker BJ;Young S;Earl AM;Kostic AD;Ojesina AI;Hasserjian R;Ballen KK;Chen YB;Hobbs G;Antin JH;Soiffer RJ;Baden LR;Garrett WS;Hornick JL;Marty FM;Meyerson M
免疫抑制与多种可能具有感染原因的特发性临床综合征相关。脐带结肠炎综合征是脐带造血干细胞移植的一种并发症，它被认为是传染性的。我们对两名脊髓性结肠炎患者的四份存档石蜡包埋内镜结肠活检标本进行了鸟枪法DNA测序。进行人类和已知微生物序列的计算减法以及将残余序列组装成细菌基因组草图。我们使用聚合酶链反应（PCR）检测和荧光原位杂交，以确定相应的细菌是否存在于其他患者和对照组。活检标本的DNA测序显示，超过250万个测序读数与已知生物体不匹配。这些序列通过计算组装成7.65 Mb的基因组草图，显示出与慢生根瘤菌属细菌基因组的高度同源性。新发现的相应细菌暂命名为Bradyrhizobium enterica。PCR鉴定为B。肠核苷酸序列，而B.在从健康对照和患有结肠癌或移植物抗宿主病的患者获得的样品中不存在肠序列。我们从脐带结肠炎患者的组织标本直接测序中组装了一个新的细菌基因组草图。这些序列与脐带结肠炎的关联提示B.肠杆菌可能是一种机会性人类病原体。（由国家癌症研究所和其他机构资助。
Immunosuppression is associated with a variety of idiopathic clinical syndromes that may have infectious causes. It has been hypothesized that the cord colitis syndrome, a complication of umbilical-cord hematopoietic stem-cell transplantation, is infectious in origin. We performed shotgun DNA sequencing on four archived, paraffin-embedded endoscopic colon-biopsy specimens obtained from two patients with cord colitis. Computational subtraction of human and known microbial sequences and assembly of residual sequences into a bacterial draft genome were performed. We used polymerase-chain-reaction (PCR) assays and fluorescence in situ hybridization to determine whether the corresponding bacterium was present in additional patients and controls. DNA sequencing of the biopsy specimens revealed more than 2.5 million sequencing reads that did not match known organisms. These sequences were computationally assembled into a 7.65-Mb draft genome showing a high degree of homology with genomes of bacteria in the bradyrhizobium genus. The corresponding newly discovered bacterium was provisionally named Bradyrhizobium enterica. PCR identified B. enterica nucleotide sequences in biopsy specimens from all three additional patients with cord colitis whose samples were tested, whereas B. enterica sequences were absent in samples obtained from healthy controls and patients with colon cancer or graft-versus-host disease. We assembled a novel bacterial draft genome from the direct sequencing of tissue specimens from patients with cord colitis. Association of these sequences with cord colitis suggests that B. enterica may be an opportunistic human pathogen. (Funded by the National Cancer Institute and others.)