Phase variation of DNA methyltransferases and the regulation of virulence and immune evasion in the pathogenic Neisseria.

Phase variation of DNA methyltransferases and the regulation of virulence and immune evasion in the pathogenic Neisseria.
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DNA甲基转移酶的相变以及致病性奈瑟菌毒力和免疫逃避的调节。

DOI:
10.1093/femspd/ftx080
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发表时间:
2017
影响因子:
3.3
通讯作者:
M. Jennings
M. Jennings
中科院分区:
医学4区
文献类型:
--
作者:
Kate L. Seib;F. Jen;A. L. Scott;A. Tan;M. Jennings

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致病奈瑟氏菌提供了阶段变化的教科书例子:基因表达的高频、随机和可逆切换。通常,在表达表面蛋白和碳水化合物结构所需的基因中观察到阶段可变基因的表达。所有淋病奈瑟菌和脑膜炎奈瑟菌都表达DNA限制修饰系统中的相变DNA甲基转移酶。这些DNA甲基转移酶(Mod)的阶段变化改变了全球DNA甲基化模式。由于阶段变化事件引起的DNA甲基化的变化改变了一组基因的表达,称为相变,并导致群体分化为具有两种不同表型的细胞。例如,在脑膜炎奈瑟氏菌中,modA11相变蛋白的转换改变了免疫原性外膜蛋白的表达,如乳铁蛋白结合蛋白,并调节了对头孢他啶和环丙沙星的敏感性。ModD1phasevarion与超强毒力脑膜炎球菌克隆性复合体相关。在淋病奈瑟氏菌中,modA13相变蛋白转换产生分化为细胞,显示出增强的生物膜形成和增强的细胞内存活。相变子广泛存在于致病奈瑟氏菌中,调节多种基因的表达。这些系统有可能影响所有关于致病性奈瑟氏菌疫苗开发和病理生物学的研究。
The pathogenic Neisseria provide textbook examples of phase variation: the high frequency, random and reversible switching of gene expression. Typically, phase variable gene expression is observed in genes required for the expression of surface proteins and carbohydrate structures. All Neisseria gonorrhoeae and N. meningitidis strains also express phase variable DNA methyltransferases that are components of DNA restriction-modification systems. Phase variation of these DNA methyltransferases (Mod) alters global DNA methylation patterns. The change in DNA methylation due to phase variation events alters expression of a regulon of genes, called a phasevarion, and results in differentiation of the population into cells with two distinct phenotypes. For example, in N. meningitidis switching of the modA11 phasevarion alters expression of immunogenic outer membrane proteins such as lactoferrin-binding protein, and also modulates sensitivity to ceftazidime and ciprofloxacin. The modD1 phasevarion is associated with hypervirulent meningococcal clonal complexes. In N. gonorrhoeae, modA13 phasevarion switching generates differentiation into cells that display enhanced biofilm formation and enhanced intracellular survival. Phasevarions are ubiquitous in pathogenic Neisseria and modulate expression of numerous genes. These systems have the potential to impact all studies on vaccine development and pathobiology in the pathogenic Neisseria.
DOI: 10.1007/978-1-61779-346-2_1
发表时间: 2012
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
作者:
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淋菌性宫颈炎:生物膜在发病机制中的作用。
DOI: 10.1086/593336
发表时间: 2008-12-15
期刊: The Journal of infectious diseases
影响因子: --
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Steichen CT;Shao JQ;Ketterer MR;Apicella MA
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发表时间: 2001-08-01
期刊: MICROBIOLOGY-SGM
影响因子: 2.8
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