Greenberg David E, Ding Li, Zelazny Adrian M, Stock Frida, Wong Alexandra, Anderson Victoria L, Miller Georgina, Kleiner David E, Tenorio Allan R, Brinster Lauren, Dorward David W, Murray Patrick R, Holland Steven M
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
PLoS Pathog. 2006 Apr;2(4):e28. doi: 10.1371/journal.ppat.0020028. Epub 2006 Apr 14.
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.
慢性肉芽肿病（CGD）是一种罕见的吞噬细胞烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶系统遗传性疾病，可导致毒性氧代谢产物产生缺陷、细菌和真菌杀伤受损以及反复发作的危及生命的感染。我们从一名CGD患者切除的淋巴结中鉴定出一种新型革兰氏阴性杆菌。革兰氏阴性杆菌在木炭酵母提取物上生长，但常规检测无法鉴定它。16S核糖体RNA（使用BLAST）的最佳50个匹配结果均为醋酸杆菌科成员，最接近的匹配是嗜糖葡糖杆菌。患者血清在全细胞裂解物免疫印迹中显示出特异性条带识别。我们使用CGD小鼠模型来确定这种微生物是否为真正的CGD病原体。与野生型小鼠相比，向gp91（phox -/-）（X连锁）和p47（phox -/-）（常染色体隐性）小鼠腹腔注射这种细菌后，基因敲除小鼠体内回收的微生物负荷更大。基因敲除小鼠的淋巴结组织病理学与我们患者的相似。我们从感染小鼠中回收了16S rRNA序列与患者原始分离株相同的微生物。我们从一名CGD患者中鉴定出一种新型革兰氏阴性杆菌。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，表明将其引入CGD小鼠而非野生型小鼠时能够引起类似疾病，并且我们从这些小鼠的病理病变中回收了相同的微生物。因此，我们满足了针对一种新病原体的科赫法则。这是首次报道由任何醋酸杆菌科引起的侵袭性人类疾病病例。多相分类分析表明这种微生物是一个新的属和种，我们提议将其命名为贝塞斯达肉芽肿杆菌。
