Adaptation by Ancient Horizontal Acquisition of Butyrate Metabolism Genes in Aggregatibacter actinomycetemcomitans.
Adaptation by Ancient Horizontal Acquisition of Butyrate Metabolism Genes in Aggregatibacter actinomycetemcomitans.
复制标题
伴放线凝聚杆菌丁酸代谢基因水平获得的适应性。
DOI：
10.1128/mbio.03581-20
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发表时间：
2021-03-23
期刊：
影响因子：
6.4
通讯作者：
Planet PJ
中科院分区：
文献类型：
--
作者：
Moustafa AM;Velusamy SK;Denu L;Narechania A;Fine DH;Planet PJ
短链脂肪酸(SCFA)对与微生物群相关的炎症效应的影响已经引起了相当大的兴趣。在这里，我们提出的证据表明，单链脂肪酸也可能是重要的疾病，通过提供能源或疾病相关的线索，以定植病原体。就像人类肠道中的细菌一样，人类口腔微生物区系中的许多物种很可能已经进化到更好地占据并坚持自己的生态位。伴生放线杆菌(Aggregatibacter Actinmycetcomitans，AA)是口腔常见的定植菌，与牙周病的发病机制密切相关。在这里，我们提出了从人类和非人类灵长类动物分离的AA分离株的全基因组系统发生分析，揭示了该物种的古老起源和与卡他犀牛的长期联系，卡他犀牛是包括东半球猴子(OWM)和人类在内的谱系。进一步的基因组分析表明，在许多人类分离株中存在一个短链脂肪酸(SCFA)分解代谢基因(AtoRDAEB)，这在几乎所有非人类OWM分离株中都是不存在的。我们认为该基因座可能是通过水平基因转移获得的。当在类似于牙周炎的牙龈下部位(厌氧，SCFA完全)的条件下生长时，带有atoRDAEB的AA菌株形成了坚固的生物膜，并显示出与毒力、定植和免疫逃避相关的基因上调。在这些条件下，同基因缺失突变体和缺乏ATO基因的非人类灵长类分离株都不能在强健的生物膜中生长，但在类似于牙周线以上的碳水化合物丰富的条件下生长良好。我们认为ATO基因的获得是一个关键的进化步骤，使AA能够利用SCFAs，适应和调节牙龈下疾病。
There has been considerable interest in the impact of short-chain fatty acids (SCFAs) on inflammatory effects related to the microbiome. Here, we present evidence that SCFAs may also be important in disease by providing an energy source or disease-associated cue for colonizing pathogens. Like the bacterial residents of the human gut, it is likely that many of the species in the human oral microbiota have evolved to better occupy and persist in their niche. Aggregatibacter actinomycetemcomitans (Aa) is both a common colonizer of the oral cavity and has been implicated in the pathogenesis of periodontal disease. Here, we present a whole-genome phylogenetic analysis of Aa isolates from humans and nonhuman primates that revealed an ancient origin for this species and a long history of association with the Catarrhini, the lineage that includes Old World monkeys (OWM) and humans. Further genomic analysis showed a strong association with the presence of a short-chain fatty acid (SCFA) catabolism locus (atoRDAEB) in many human isolates that was absent in almost all nonhuman OWM isolates. We show that this locus was likely acquired through horizontal gene transfer. When grown under conditions that are similar to those at the subgingival site of periodontitis (anaerobic, SCFA replete), Aa strains with atoRDAEB formed robust biofilms and showed upregulation of genes involved in virulence, colonization, and immune evasion. Both an isogenic deletion mutant and nonhuman primate isolates lacking the ato locus failed to grow in a robust biofilm under these conditions, but grew well under the carbohydrate-rich conditions similar to those found above the gumline. We propose that the acquisition of the ato locus was a key evolutionary step allowing Aa to utilize SCFAs, adapt, and modulate subgingival disease.