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Genomic and Global Approaches to Unravelling How Hypermutable Sequences Influence Bacterial Pathogenesis

机译：揭示超可变序列如何影响细菌发病机理的基因组和全局方法

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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.
机译：快速适应宿主环境中的波动有助于细菌病原体的宿主持久性和毒力。适应通常由细菌病原体中的高变序列介导。早期的细菌基因组研究确定了这些高变序列的多样性和与毒力相关的功能。因此，发现简单的序列重复道（SSR）和位点特异性重组可以控制荚膜类型，脂多糖结构，菌毛蛋白多样性和外膜蛋白的表达。我们回顾了如何通过疾病分离株的全基因组序列研究，临床样品分析和模型系统的使用来揭示SSR介导的局部超突变机制中固有的种群多样性。在下一代测序数据中分析简单序列重复的问题性质与更简单，实用的基于PCR的方法之间存在问题性的对比。给出了一些具体例子，说明这种局部性超突变与脑膜炎球菌发病机理的潜在相关性。这使我们推测未来的前景，以阐明高变机制如何有助于细菌病原体的传播，传播和持久性。

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