Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae

Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae
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DOI:
10.1128/iai.68.4.2082-2095.2000
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发表时间:
2000-04-01
影响因子:
3.1
通讯作者:
Tinsley, CR
Tinsley, CR
中科院分区:
医学2区
文献类型:
--
作者:
Klee, SR;Nassif, X;Tinsley, CR

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致病性脑膜炎奈瑟氏菌和淋病奈瑟氏菌引起显著不同的疾病,尽管在遗传和生化水平上有很强的相关性。N.脑膜炎可以穿过血脑屏障引起脑膜炎,并且与N.淋病我们以前使用消减杂交来鉴定可能编码菌血症和脑膜侵袭特异性功能的DNA序列,因为它们是N.脑膜炎球菌和脑膜炎奈瑟菌缺席。淋病在这份报告中,我们表明,这些序列标记8个遗传岛,大小范围从1.8到40 kb,其染色体位置是恒定的。这些遗传岛中的五个在一组代表性的菌株中是保守的和/或携带与已知毒力同源的基因。其他物种的因素。这些被删除,并在体外和体内的毒力相关的突变体进行了测试。这一策略确定了一个岛,区域8,这是需要在脑膜炎球菌感染的幼鼠模型中诱导菌血症。区域8编码推定的铁载体受体和二硫键氧化还原酶。没有一个缺失的突变体在其对血清杀菌作用的抗性方面被修饰。突变株与内皮细胞相互作用的能力也没有改变,这表明这种相互作用不是由N.脑膜炎
The pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae cause dramatically different diseases despite strong relatedness at the genetic and biochemical levels. N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. gonorrhoeae. We previously used subtractive hybridization to identify DNA sequences which might encode functions specific to bacteremia and invasion of the meninges because they are specific to N. meningitidis and absent from N. gonorrhoeae. In this report we show that these sequences mark eight genetic islands that range in size from 1.8 to 40 kb and whose chromosomal location is constant. Five of these genetic islands were conserved within a representative set of strains and/or carried genes with homologies to known virulence. factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy identified one island, region 8, which is needed to induce bacteremia in an infant rat model of meningococcal infection. Region 8 encodes a putative siderophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neither were the mutant strains altered in their ability to interact with endothelial cells, suggesting that such interactions are not encoded by large genetic islands in N. meningitidis.