Fusobacterium nucleatum is an anaerobic commensal of the oral cavity associated with periodontitis and extra-oral diseases, including colorectal cancer. Previous studies have shown an increased relative abundance of this bacterium associated with oral dysplasia or within oral tumours. Using direct culture, we found that 75 % of Fusobacterium species isolated from malignant or potentially malignant oral mucosa were F. nucleatum subsp. polymorphum. Whole genome sequencing and pangenome analysis with Panaroo was carried out on 76 F. nucleatum subsp. polymorphum genomes. F. nucleatum subsp. polymorphum was shown to possesses a relatively small core genome of 1604 genes in a pangenome of 7363 genes. Phylogenetic analysis based on the core genome shows the isolates can be separated into three main clades with no obvious genotypic associations with disease. Isolates recovered from healthy and diseased sites in the same patient are generally highly related. A large repertoire of adhesins belonging to the type V secretion system (TVSS) could be identified with major variation in repertoire and copy number between strains. Analysis of intergenic recombination using fastGEAR showed that adhesin complement is shaped by horizontal gene transfer and recombination. Recombination events at TVSS adhesin genes were not only common between lineages of subspecies polymorphum, but also between different subspecies of F. nucleatum. Strains of subspecies polymorphum with low copy numbers of TVSS adhesin encoding genes tended to have the weakest adhesion to oral keratinocytes. This study highlights the genetic heterogeneity of F. nucleatum subsp. polymorphum and provides a new framework for defining virulence in this organism.

中文翻译：

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有核梭杆菌亚种从恶性和潜在恶性口腔疾病中恢复的多态性在粘附表型和粘附素基因拷贝数方面表现出异质性，由亚种间水平基因转移和重组衍生的嵌合体形成

具核梭杆菌是一种口腔厌氧共生菌，与牙周炎和口腔外疾病（包括结直肠癌）相关。先前的研究表明，这种细菌的相对丰度增加与口腔发育不良或口腔肿瘤内相关。通过直接培养，我们发现从恶性或潜在恶性口腔粘膜中分离出的梭杆菌属物种中 75% 是具核梭杆菌亚种。多态性。 Panaroo 在 76 F上进行了全基因组测序和泛基因组分析。有核亚种多态基因组。F. nucleatum subsp.研究表明，多态性在 7363 个基因的全基因组中拥有相对较小的 1604 个基因的核心基因组。基于核心基因组的系统发育分析表明，分离株可分为三个主要分支，与疾病没有明显的基因型关联。从同一患者的健康部位和患病部位回收的分离株通常高度相关。属于 V 型分泌系统 (TVSS) 的大量粘附素可以被识别，并且菌株之间的成分和拷贝数存在重大差异。使用 fastGEAR 对基因间重组的分析表明，粘附素补体是通过水平基因转移和重组形成的。 TVSS粘附素基因的重组事件不仅在多形亚种谱系之间常见，而且在具核梭杆菌不同亚种之间也很常见。具有低拷贝数 TVSS 粘附素编码基因的多形亚种菌株往往对口腔角质形成细胞的粘附最弱。这项研究强调了F. nucleatum subsp.的遗传异质性。多态性并为定义该生物体的毒力提供了新的框架。