Brain damage in newborn rat model of meningitis by Enterobacter sakazakii: a role for outer membrane protein A.
Brain damage in newborn rat model of meningitis by Enterobacter sakazakii: a role for outer membrane protein A.
复制标题
DOI：
10.1038/labinvest.2008.164
复制
发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
坂崎肠杆菌 (ES) 是一种新出现的病原体，可引起新生儿败血症、脑膜炎和坏死性小肠结肠炎。关于这些疾病的发病机制和 ES 的特定毒力因子的信息非常有限。在这里，我们首次使用新生大鼠模型证明，外膜蛋白 A (OmpA) 的表达对于 ES 引起的脑膜炎的发生很重要。口服 OmpA+ ES 穿过肠屏障，在血液中繁殖，随后穿透血脑屏障。 OmpA+ ES 在受感染动物的大脑中大量存在，并伴有相关的中性粒细胞浸润、出血和神经胶质增生。相反，OmpA-ES在体外和体内均不能有效结合肠上皮细胞。结合的 OmpA+ ES 还会引起感染动物肠段中肠细胞的凋亡； OmpA− ES 没有。此外，OmpA− ES 非常容易被血液和血清杀死，而 OmpA+ ES 具有抵抗力。值得注意的是，OmpA+ ES 感染的新生大鼠死亡率为 100%，而 OmpA− ES 感染的大鼠存活且没有任何病理表现。通过与 ompA 基因互补，OmpA− ES 无法引起疾病。这些结果表明，ES 中的 OmpA 表达对于胃肠道定植以及随后在血液中存活以引起脑膜炎是必需的。
Enterobacter sakazakii(ES) is an emerging pathogen that causes sepsis, meningitis, and necrotizing enterocolitis in neonates. Very limited information is available regarding the pathogenesis of these diseases and the specific virulence factors of ES. Here, we demonstrate, for the first time using a newborn rat model, that outer membrane protein A (OmpA) expression is important for the onset of meningitis by ES. Orally administered OmpA+ ES traverses the intestinal barrier, multiplies in blood, and subsequently penetrates the blood-brain barrier. OmpA+ ES were present in high numbers in the brains of infected animals along with associated neutrophil infiltration, hemorrhage, and gliosis. In contrast, OmpA− ES could not bind to the intestinal epithelial cells in vitro and in vivo efficiently. The bound OmpA+ ES also caused apoptosis of enterocytes in the intestinal segments of infected animals; OmpA− ES did not. Furthermore, OmpA− ES is very susceptible to blood and serum killing whereas OmpA+ ES is resistant. Of note, 100% mortality rates were observed in OmpA+ ES infected newborn rats while OmpA− ES infected rats survived without any pathological manifestations. The inability of OmpA− ES to cause disease was restored by complementation with the ompA gene. These results suggest that OmpA expression in ES is necessary for the colonization of the gastrointestinal tract and for subsequent survival in blood to cause meningitis.
登录
查看更多内容
影响因子：
9.4
作者：
MUYTJENS, HL;ZANEN, HC;FARMER, JJ
通讯作者：
FARMER, JJ
影响因子：
3.1
作者：
HUANG, SH;WASS, C;KIM, KS
通讯作者：
KIM, KS
影响因子：
11.1
作者：
Gehre, F.;Leib, S. L.;Tomasz, A.
通讯作者：
Tomasz, A.
影响因子：
2.2
作者：
Çaksen, H;Cemek, M;Cemek, F
通讯作者：
Cemek, F
影响因子：
3.1
作者：
Prasadarao, NV;Wass, CA;Kim, KS
通讯作者：
Kim, KS