University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
mSphere. 2020 Nov 18;5(6):e00799-20. doi: 10.1128/mSphere.00799-20.
Illness caused by the pathogen is widespread and can range in severity from mild diarrhea to sepsis and death. Strains of isolated from human infections exhibit great genetic diversity, leading to the hypothesis that the genetic background of the infecting strain at least partially determines a patient's clinical course. However, although certain strains of have been suggested to be associated with increased severity, strain typing alone has proved insufficient to explain infection severity. The limited explanatory power of strain typing has been hypothesized to be due to genetic variation within strain types, as well as genetic elements shared between strain types. Homologous recombination is an evolutionary mechanism that can result in large genetic differences between two otherwise clonal isolates, and also lead to convergent genotypes in distantly related strains. More than 400 genomes were analyzed here to assess the effect of homologous recombination within and between clades. Almost three-quarters of single nucleotide variants in the phylogeny are predicted to be due to homologous recombination events. Furthermore, recombination events were enriched in genes previously reported to be important to virulence and host-pathogen interactions, such as flagella, cell wall proteins, and sugar transport and metabolism. Thus, by exploring the landscape of homologous recombination in , we identified genetic loci whose elevated rates of recombination mediated diversification, making them strong candidates for being mediators of host-pathogen interaction in diverse strains of Infections with result in up to half a million illnesses and tens of thousands of deaths annually in the United States. The severity of illness is dependent on both host and bacterial factors. Studying the evolutionary history of pathogens is important for understanding the variation in pathogenicity of these bacteria. This study examines the extent and targets of homologous recombination, a mechanism by which distant strains of bacteria can share genetic material, in hundreds of strains and identifies hot spots of realized recombination events. The results of this analysis reveal the importance of homologous recombination in the diversification of genetic loci in that are significant in its pathogenicity and host interactions, such as flagellar construction, cell wall proteins, and sugar transport and metabolism.
由病原体引起的疾病广泛存在，其严重程度从轻到重不等，从轻度腹泻到败血症和死亡不等。从人类感染中分离出的菌株表现出很大的遗传多样性，这导致了这样的假设，即感染菌株的遗传背景至少部分决定了患者的临床过程。然而，尽管某些 菌株已被认为与严重程度增加有关，但仅菌株分型已被证明不足以解释感染的严重程度。菌株分型解释能力有限的假设是由于菌株类型内的遗传变异以及菌株类型之间的遗传元件共享。同源重组是一种进化机制，它可以导致两个原本克隆的分离株之间产生很大的遗传差异，也可以导致远缘菌株产生趋同基因型。在这里，分析了超过 400 个基因组，以评估 内和 之间同源重组的影响。 系统发育中的近四分之三的单核苷酸变体预计是由于同源重组事件。此外，重组事件在以前报道对毒力和宿主-病原体相互作用很重要的基因中富集，例如鞭毛、细胞壁蛋白以及糖的运输和代谢。因此，通过探索 中的同源重组景观，我们确定了遗传基因座，其重组介导的多样化程度升高，使它们成为不同 菌株中宿主-病原体相互作用的重要调节因子。 在美国，每年有多达 50 万人患病，数万人死亡。 的严重程度取决于宿主和细菌因素。研究 病原体的进化历史对于理解这些细菌致病性的变化很重要。本研究检查了数百个 菌株中同源重组的程度和目标，这是一种细菌可以共享遗传物质的机制，并确定了已实现重组事件的热点。该分析的结果揭示了同源重组在 中与致病性和宿主相互作用相关的遗传基因座多样化中的重要性，例如鞭毛结构、细胞壁蛋白以及糖的运输和代谢。
