Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis.
Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis.
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DOI：
10.1186/s40168-023-01607-w
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发表时间：
2023-07-25
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
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牙龈卟啉单胞菌（Porphyromonas gingivalis，以下称为“Pg”）是一种口腔病原体，其被假设为炎症和牙周病的关键驱动因素。虽然Pg是最容易从积极进展的牙周病，健康的个人和那些稳定的非进展性疾病的个人恢复也殖民化的Pg。深入了解的因素，形成惊人的应变水平变化的Pg，其变量与疾病的关联，需要实现一个更机械的了解牙周病及其进展。在微生物群落中形成菌株水平多样性的关键力量之一是细菌被其病毒（噬菌体）捕食者和共生体感染。令人惊讶的是，虽然PG已超过40年的研究主题，基本上是什么都不知道的，它的寄生虫，和流行的范式是，寄生虫是不重要的生态PG。在这里，我们系统地解决了这个问题，是否PG被感染的噬菌体，我们发现，他们是。我们发现，原噬菌体在Pg中很常见，它们是基因组多样性的，它们编码的基因有可能改变Pg的生理和相互作用。我们发现，Pg中的CRISPR-Cas防御系统的未识别的靶标代表了Pg中普遍存在的CRISPR-Cas防御系统，并且Pg菌株编码许多另外的机制上不同的候选抗噬菌体防御系统。我们还发现，噬菌体和候选抗噬菌体防御系统元件一起是这种口腔病原体的菌株水平多样性和物种泛基因组的主要贡献者。最后，我们证明了由模型Pg菌株所携带的原噬菌体在培养中是活跃的，在肉汤培养物中产生细胞外病毒颗粒。这项工作明确地确定了噬菌体是一种主要的未被认识到的力量，它塑造了研究充分的口腔病原体Pg的生态学和种内菌株水平的多样性。我们在这里建立的基础噬菌体序列数据集和模型系统增加了所有已知的关于Pg的丰富背景，并指出了未来研究的许多途径，这些途径有望为噬菌体对人类健康和疾病的广泛影响的基本特征提供新的线索。视频摘要在线版本包含补充材料，可通过10. 1186/s40168-023-01607-w获取。
Porphyromonas gingivalis (hereafter “Pg”) is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. One of the key forces often shaping strain-level diversity in microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg. Here we systematically addressed the question of whether Pg are infected by phages—and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain-level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures. This work definitively establishes that phages are a major unrecognized force shaping the ecology and intra-species strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly. Video Abstract The online version contains supplementary material available at 10.1186/s40168-023-01607-w.
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DOI：
10.1073/pnas.1305923110
发表时间：
2013-06-25
影响因子：
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作者：
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通讯作者：
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