A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease
A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease
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DOI：
10.1382/journal.ppat.0020028
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发表时间：
2006-04-01
期刊：
影响因子：
6.7
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
--
作者：
Greenberg, David E.;Ding, Li;Holland, Steven M.
慢性肉芽肿病（CGD）是一种罕见的吞噬细胞NADPH氧化酶系统的遗传性疾病，导致有毒氧代谢产物的产生缺陷，细菌和真菌的杀伤受损，以及危及生命的反复感染。我们在一例CGD患者的切除淋巴结中发现了一种新的革兰氏阴性杆菌。革兰氏阴性杆菌生长在木炭-酵母提取物上，但常规测试无法识别它。16 S rRNA的最佳50个匹配（使用BLAST）都是Acetocellulaceae家族的成员，最接近的匹配是Gluconocellulsacchari。患者血清在全裂解物免疫印迹中显示特异性条带识别。我们使用CGD小鼠模型来确定这种生物体是否是真正的CGD病原体。腹膜内注射gp 91（phox-/）-（X连锁）和p47（phox-/）-（常染色体隐性遗传）小鼠与野生型小鼠相比，该细菌导致更大的负担，从敲除回收的有机体。敲除小鼠淋巴结的组织病理学与我们患者中观察到的相似。我们从受感染的小鼠中回收了16 S rRNA序列与患者原始分离物相同的微生物。我们从一例CGD患者中发现了一种新的革兰氏阴性杆菌。为了证实其致病性，我们通过高滴度抗体证明了特异性免疫反应，表明当引入CGD而不是野生型小鼠时，它能够引起类似的疾病，并且我们从这些小鼠的病理损伤中回收了相同的生物体。因此，我们已经满足了科赫对一种新病原体的假设。这是第一次报告的情况下，侵入性人类疾病引起的任何醋粟科。多相分类学分析表明，这种生物是一个新的属和种，我们建议的名称颗粒杆菌bethesdensis。
Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system causing defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections. We identified a novel gram-negative rod in excised lymph nodes from a patient with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST) were all members of the family Acetobacteraceae, with the closest match being Gluconobacter sacchari. Patient serum showed specific band recognition in whole lysate immunoblot. We used mouse models of CGD to determine whether this organism was a genuine CGD pathogen. Intraperitoneal injection of gp91(phox-/)-(X-linked) and p47(phox-/)-(autosomal recessive) mice with this bacterium led to larger burdens of organism recovered from knockout compared with wild-type mice. Knockout mouse lymph nodes had histopathology that was similar to that seen in our patient. We recovered organisms with 16S rRNA sequence identical to the patient's original isolate from the infected mice. We identified a novel gram-negative rod from a patient with CGD. To confirm its pathogenicity, we demonstrated specific immune reaction by high titer antibody, showed that it was able to cause similar disease when introduced into CGD, but not wild-type mice, and we recovered the same organism from pathologic lesions in these mice. Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the first reported case of invasive human disease caused by any of the Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new genus and species for which we propose the name Granulobacter bethesdensis.