Illness caused by the pathogen Clostridioides difficile is widespread and can range in severity from mild diarrhea to sepsis and death. Strains of C. difficile 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 C. difficile 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 C. difficile genomes were analyzed here to assess the effect of homologous recombination within and between C. difficile clades. Almost three-quarters of single nucleotide variants in the C. difficile 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 C. difficile, 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 C. difficile.

中文翻译：

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艰难梭菌中的同源重组介导细胞表面特征和运输系统的多样化

由病原体艰难梭菌引起的疾病很普遍，严重程度从轻度腹泻到败血症和死亡不等。从人类感染中分离的艰难梭菌菌株表现出很大的遗传多样性，从而导致假设感染菌株的遗传背景至少部分决定了患者的临床病程。然而，虽然某些艰难梭菌菌株已被认为与严重程度增加有关，但单独的菌株分型已证明不足以解释感染的严重程度。菌株分型的有限解释力被假设是由于菌株类型内的遗传变异以及菌株类型之间共享的遗传元件。同源重组是一种进化机制，它可以导致两个其他克隆分离株之间的巨大遗传差异，并且还会导致远缘相关菌株的基因型趋同。这里分析了 400 多个艰难梭菌基因组，以评估艰难梭菌进化枝内部和之间同源重组的影响。艰难梭菌中几乎四分之三的单核苷酸变异系统发育被预测是由于同源重组事件。此外，重组事件富含先前报道的对毒力和宿主-病原体相互作用很重要的基因，例如鞭毛、细胞壁蛋白以及糖的转运和代谢。因此，通过探索艰难梭菌同源重组的景观，我们确定了重组率升高介导多样化的基因位点，使它们成为不同艰难梭菌菌株中宿主-病原体相互作用的介质的有力候选者。