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Abstract：
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.
摘要：
核梭杆菌是与牙周炎和口腔外疾病相关的口腔厌氧共生菌，包括结直肠癌.先前的研究表明，与口腔发育不良或口腔肿瘤相关的这种细菌的相对丰度增加。使用直接文化，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有75％是F.nucleatum亚种。多晶型物。在76F.核仁亚种上使用Panaroo进行全基因组测序和pangenome分析。多晶型基因组。F.核仁亚种。在7363个基因的pangenome中，多态性被证明具有1604个基因的相对较小的核心基因组。基于核心基因组的系统发育分析表明，分离株可以分为三个主要分支，与疾病没有明显的基因型关联。从同一患者的健康和患病部位回收的分离物通常高度相关。可以鉴定属于V型分泌系统（TVSS）的大量粘附素，其菌株之间的库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而形成的。TVSS粘附素基因的重组事件不仅在多态性亚种谱系之间常见，而且在F.核仁的不同亚种之间。具有低拷贝数TVSS粘附素编码基因的亚种多态性菌株倾向于对口腔角质形成细胞的粘附力最弱。这项研究强调了F.nucleatum亚种的遗传异质性。多晶型物，并为定义该生物体的毒力提供了新的框架。
