PDF(Pubmed)
Abstract：
Comensal Bacteroidota (Bacteroidota) and Enterobacteriacea are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism in Bacteroidota remain unclear. By using the classical lipopolysaccharide/O-antigen \'rfb operon\' in Enterobacteriaceae as a surface antigen model (5-rfb-gene-cluster rfbABCDX), and a recent rfbA-typing strategy for strain classification, we characterized the integrity and conservancy of the entire rfb operon in Bacteroidota. Through exploratory analysis of complete genomes and metagenomes, we discovered that most Bacteroidota have the rfb operon fragmented into nonrandom patterns of gene-singlets and doublets/triplets, termed \'rfb-gene-clusters\', or rfb-\'minioperons\' if predicted as transcriptional. To reflect global operon integrity, contiguity, duplication, and fragmentation principles, we propose a six-category (infra/supra-numerary) cataloging system and a Global Operon Profiling System for bacteria. Mechanistically, genomic sequence analyses revealed that operon fragmentation is driven by intra-operon insertions of predominantly Bacteroides-DNA (thetaiotaomicron/fragilis) and likely natural selection in gut-wall specific micro-niches or micropathologies. Bacteroides-insertions, also detected in other antigenic operons (fimbriae), but not in operons deemed essential (ribosomal), could explain why Bacteroidota have fewer KEGG-pathways despite large genomes. DNA insertions, overrepresenting DNA-exchange-avid (Bacteroides) species, impact our interpretation of functional metagenomics data by inflating by inflating gene-based pathway inference and by overestimating \'extra-species\' abundance. Of disease relevance, Bacteroidota species isolated from cavitating/cavernous fistulous tract (CavFT) microlesions in Crohn\'s Disease have supra-numerary fragmented operons, stimulate TNF-alpha from macrophages with low potency, and do not induce hyperacute peritonitis in mice compared to CavFT Enterobacteriaceae. The impact of \'foreign-DNA\' insertions on pro-inflammatory operons, metagenomics, and commensalism/opportunism requires further studies to elucidate their potential for novel diagnostics and therapeutics, and to elucidate the role of co-existing pathobionts in Crohn\'s disease microlesions.
摘要：
共生拟杆菌（Bacteroidota）和肠杆菌通常与肠道炎症有关。然而,影响拟杆菌肠道共生/机会二元论的促炎表面抗原变异性的原因尚不清楚.通过使用肠杆菌科的经典脂多糖/O-抗原“rfb操纵子”作为表面抗原模型（5-rfb基因簇rfbABCDX），以及最近的一种用于菌株分类的rfbA分型策略，我们描述了拟杆菌整个rfb操纵子的完整性和完整性。通过对完整基因组和宏基因组的探索性分析，我们发现大多数拟杆菌的rfb操纵子被分解成非随机模式的基因-单染色体和双染色体/三胞胎，称为“rfb-基因簇”，或rfb-“小操纵子”，如果预测为转录。为了反映全球操纵子的完整性，连续性，重复，和碎片化原则，我们提出了一个六类（下/超数字）编目系统和一个用于细菌的全球操纵子分析系统。机械上,基因组序列分析显示，操纵子片段化是由主要是拟杆菌DNA（thetaotaomicron/fragilis）的操纵子内插入以及肠壁特异性微生态位或微病理中可能的自然选择驱动的。拟杆菌插入，也在其他抗原操纵子（菌毛）中检测到，但不是在被认为是必需的操纵子（核糖体）中，可以解释为什么尽管基因组很大，但类杆菌的KEGG途径却较少。DNA插入,过度代表DNA交换狂热（拟杆菌）物种，通过膨胀基于基因的途径推断和高估“物种外”丰度来影响我们对功能宏基因组学数据的解释。与疾病相关，从克罗恩病的空化/海绵状瘘管（CavFT）微病变中分离出的拟杆菌物种具有超数片段化操纵子，从低效力的巨噬细胞中刺激TNF-α，与CavFT肠杆菌科相比，不会在小鼠中引起急性腹膜炎。外源DNA插入对促炎操纵子的影响，宏基因组学，和共生主义/机会主义需要进一步的研究，以阐明其对新型诊断和治疗的潜力，并阐明共存的病原体在克罗恩病微病变中的作用。
