IDENTIFICATION OF THE UNCULTURED BACILLUS OF WHIPPLES DISEASE

IDENTIFICATION OF THE UNCULTURED BACILLUS OF WHIPPLES DISEASE
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DOI:
10.1056/nejm199207303270501
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发表时间:
1992-07-30
影响因子:
158.5
通讯作者:
FALKOW, S
FALKOW, S
中科院分区:
医学1区
文献类型:
--
作者:
RELMAN, DA;SCHMIDT, TM;FALKOW, S

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背景维普莱病是一种全身性疾病,85年来一直被认为与未培养的,因此未鉴定的杆菌有关。我们用分子遗传学的方法来鉴定这种生物。通过聚合酶链反应,首先用宽范围引物,然后用特异性引物,直接从5名不相关的维普莱病患者的组织中扩增细菌16 S核糖体RNA(rRNA)序列。对扩增产物进行核苷酸序列测定和分析。一个独特的1321碱基的细菌16S rRNA序列从一个病人的十二指肠组织扩增。这一序列表明存在一种以前未鉴定的生物体。然后,我们在所有5名维普莱病患者的组织中检测到该序列,但在10名非惠普尔病患者的组织中没有检测到该序列。系统发育分析表明,该菌为革兰氏阳性放线菌,与已知属的亲缘关系不近。我们已经鉴定出与维普莱病有关的未培养的杆菌。这种细菌的系统发育关系,其独特的形态特征,和不寻常的功能的疾病是足够的理由命名此芽孢杆菌Tropheryma whippelii gen. nov. sp. nov.我们的研究结果也提供了一个特定的诊断测试,这种生物体的基础。
Background. Whipple's disease is a systemic disorder known for 85 years to be associated with an uncultured, and therefore unidentified, bacillus.Methods. We used a molecular genetic approach to identify this organism. The bacterial 16S ribosomal RNA (rRNA) sequence was amplified directly from tissues of five unrelated patients with Whipple's disease by means of the polymerase chain reaction, first with broad-range primers and then with specific primers. We determined and analyzed the nucleotide sequence of the amplification products.Results. A unique 1321-base bacterial 16S rRNA sequence was amplified from duodenal tissue of one patient. This sequence indicated the presence of a previously un characterized organism. We then detected this sequence in tissues from all 5 patients with Whipple's disease, but in none of those from 10 patients without the disorder. According to phylogenetic analysis, this bacterium is a gram-positive actinomycete that is not closely related to any known genus.Conclusions. We have identified the uncultured bacillus associated with Whipple's disease. The phylogenetic relations of this bacterium, its distinct morphologic characteristics, and the unusual features of the disease are sufficient grounds for naming this bacillus Tropheryma whippelii gen. nov. sp. nov. Our findings also provide a basis for a specific diagnostic test for this organism.