Division of Pediatric Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA.
mBio. 2021 Mar 23;12(2):e03581-20. doi: 10.1128/mBio.03581-20.
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. () 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 isolates from humans and nonhuman primates that revealed an ancient origin for this species and a long history of association with the , 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 () 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), strains with 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 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 locus was a key evolutionary step allowing to utilize SCFAs, adapt, and modulate subgingival disease. 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. We propose that SCFAs allow () to adapt to the subgingival anaerobic environment, which is the site of human periodontitis. Under anaerobic, SCFA-rich conditions, human-derived strains that possess butyrate metabolism genes form strong biofilms and upregulate virulence genes. Our phylogenetic analysis highlights a long history of evolution of with its primate hosts and suggests that the acquisition of butyrate metabolism genes may have been a critical step in allowing to colonize a new niche and cause disease in humans. Overall, this study highlights the important role that horizontal gene transfer may play in microbial adaptation and the evolution of infectious disease.
与人类肠道中的细菌居民一样,人类口腔微生物群中的许多物种可能已经进化为更好地占据和维持其生态位。()是口腔中的常见定植菌,并与牙周病的发病机制有关。在这里,我们对来自人类和非人类灵长类动物的分离株进行了全基因组系统发育分析,结果表明该物种起源于远古时期,与包括旧世界猴(OWM)和人类在内的谱系有着悠久的联系。进一步的基因组分析表明,在许多人类分离株中存在与短链脂肪酸(SCFA)代谢基因座()存在强烈关联,而在几乎所有非人类 OWM 分离株中都不存在。我们表明,该基因座可能是通过水平基因转移获得的。当在类似于牙周炎龈下部位的条件下(厌氧、富含 SCFA)生长时,带有 的菌株形成了强大的生物膜,并表现出与毒力、定植和免疫逃避相关的基因上调。在这些条件下,缺失 基因座的同基因缺失突变体和非人类灵长类动物分离株都无法形成强大的生物膜,但在类似于龈上发现的富含碳水化合物的条件下生长良好。我们提出,获得 基因座是使 利用 SCFA、适应和调节龈下疾病的关键进化步骤。人们对短链脂肪酸(SCFAs)对与微生物组相关的炎症影响的影响非常感兴趣。在这里,我们提供的证据表明,SCFAs 也可能通过为定植病原体提供能量来源或与疾病相关的线索在疾病中发挥重要作用。我们提出,SCFAs 使 ()适应龈下厌氧环境,这是人类牙周炎的部位。在厌氧、富含 SCFA 的条件下,具有丁酸代谢基因的人类来源的 菌株形成强大的生物膜并上调毒力基因。我们的系统发育分析突出了 与其灵长类宿主之间的悠久进化历史,并表明丁酸代谢基因的获得可能是 定植新生态位并在人类中引起疾病的关键步骤。总的来说,这项研究强调了水平基因转移在微生物适应和传染病进化中可能发挥的重要作用。