Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli
Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli
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DOI：
10.1086/430614
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发表时间：
2005-07-01
影响因子：
6.4
通讯作者：
Kaplan, G
中科院分区：
文献类型：
--
作者：
Tsenova, L;Ellison, E;Kaplan, G
人类感染结核分枝杆菌会导致大约 10% 的免疫功能正常的个体出现活动性疾病，当杆菌感染中枢神经系统 (CNS) 时，会出现最严重的临床表现。在这里，我们使用结核性脑膜炎兔模型来评估结核分枝杆菌临床分离株CDC1551（一种高免疫原性菌株）和HN878或W4（W/北京菌株家族的2个成员）引起的疾病的严重程度。与感染CDC1551相比，中枢神经系统感染HN878或W4会导致脑脊液和大脑中的杆菌载量更高，杆菌向其他器官的播散增加，肿瘤坏死因子-a持续水平升高，白细胞升高，临床表现更严重。这种致病过程与 HN878 产生聚酮合酶衍生的酚糖脂 (PGL) 相关，感染 pks1-15 基因（PGL 合成所需）的 HN878 突变体的兔子的毒力降低就证明了这一点。
Infection with Mycobacterium tuberculosis in humans results in active disease in similar to 10% of immune-competent individuals, with the most-severe clinical manifestations observed when the bacilli infect the central nervous system (CNS). Here, we use a rabbit model of tuberculous meningitis to evaluate the severity of disease caused by the M. tuberculosis clinical isolates CDC1551, a highly immunogenic strain, and HN878 or W4, 2 members of the W/Beijing family of strains. Compared with infection with CDC1551, CNS infection with HN878 or W4 resulted in higher bacillary loads in the cerebrospinal fluid and brain, increased dissemination of bacilli to other organs, persistent levels of tumor necrosis factor-a, higher leukocytosis, and more-severe clinical manifestations. This pathogenic process is associated with the production by HN878 of a polyketide synthase derived phenolic glycolipid (PGL), as demonstrated by reduced virulence in rabbits infected with an HN878 mutant disrupted in the pks1-15 gene, which is required for PGL synthesis.