Genomic and global approaches to unravelling how hypermutable sequences influence bacterial pathogenesis.
Genomic and global approaches to unravelling how hypermutable sequences influence bacterial pathogenesis.
复制标题
DOI：
10.3390/pathogens3010164
复制
发表时间：
2014-02-25
期刊：
影响因子：
--
通讯作者：
Bayliss CD
中科院分区：
文献类型：
--
作者：
Bidmos FA;Bayliss CD
对宿主环境波动的快速适应有助于宿主的持久性和细菌病原体的毒力。在细菌病原体中，适应性通常由超可变序列介导。早期的细菌基因组研究确定了这些超可变序列的多样性和毒力相关功能。因此，简单序列重复束（SSRs）和位点特异性重组控制着荚膜类型、脂多糖结构、绒毛蛋白多样性和外膜蛋白的表达。我们回顾了ssr介导的局部超突变机制中固有的种群多样性是如何通过对疾病分离物全基因组序列的调查、临床样本的分析和模型系统的使用来解锁的。在分析下一代测序数据中简单序列重复的问题性质和更简单、实用的基于pcr的方法之间提出了对比。具体的例子提出了这种局部高突变与脑膜炎球菌发病机制的潜在相关性。这让我们推测未来的前景，揭示超可变机制如何有助于细菌病原体的传播、传播和持续存在。
Rapid adaptation to fluctuations in the host milieu contributes to the host persistence and virulence of bacterial pathogens. Adaptation is frequently mediated by hypermutable sequences in bacterial pathogens. Early bacterial genomic studies identified the multiplicity and virulence-associated functions of these hypermutable sequences. Thus, simple sequence repeat tracts (SSRs) and site-specific recombination were found to control capsular type, lipopolysaccharide structure, pilin diversity and the expression of outer membrane proteins. We review how the population diversity inherent in the SSR-mediated mechanism of localised hypermutation is being unlocked by the investigation of whole genome sequences of disease isolates, analysis of clinical samples and use of model systems. A contrast is presented between the problematical nature of analysing simple sequence repeats in next generation sequencing data and in simpler, pragmatic PCR-based approaches. Specific examples are presented of the potential relevance of this localized hypermutation to meningococcal pathogenesis. This leads us to speculate on the future prospects for unravelling how hypermutable mechanisms may contribute to the transmission, spread and persistence of bacterial pathogens.