Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Los Angeles, California, USA.
mBio. 2012 Sep 25;3(5). doi: 10.1128/mBio.00279-12. Print 2012.
Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.
Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.
对人类微生物组的研究揭示了在不同解剖部位存在多样且复杂的微生物群落。人类皮脂腺的微生物组为研究其主要细菌居民痤疮丙酸杆菌提供了一个可行的模型，据认为痤疮丙酸杆菌有助于人类疾病痤疮的发病机制。为了探索感染痤疮丙酸杆菌的噬菌体的多样性，从皮肤健康或痤疮供体的皮脂腺中分离出 11 株痤疮丙酸杆菌噬菌体，并对其基因组进行测序。对跨越 30 年时间和广泛地理范围的痤疮丙酸杆菌噬菌体群体的比较基因组分析表明，在基因组长度、GC 含量百分比、核苷酸同一性（>85%）和基因含量方面具有惊人的相似性。鉴于在几乎所有其他噬菌体群体中观察到的广泛多样性，这是出乎意料的。尽管痤疮丙酸杆菌噬菌体对临床分离株的宿主范围很广，但有两种细菌分离株对许多这些噬菌体具有抗性。此外，噬菌体抗性模式与细菌中存在的聚类规则间隔短回文重复元件密切相关，这些元件针对特定的噬菌体亚群，赋予了原核先天免疫系统。痤疮丙酸杆菌噬菌体的多样性有限，这可能与它们的细菌宿主所在的富含脂质的厌氧环境所施加的独特进化限制有关，这表明基于噬菌体的抗菌治疗痤疮的潜力。
痤疮丙酸杆菌是皮肤微生物群的主要成员，也与痤疮的发病机制有关；然而，对于与这种细菌共存并感染这种细菌的噬菌体知之甚少。在这里，我们介绍了 11 株痤疮丙酸杆菌噬菌体的新型基因组序列，从而大大增加了有关该噬菌体群体的可用基因组信息的数量。令人惊讶的是，我们发现与其他研究充分的噬菌体不同，痤疮丙酸杆菌噬菌体高度同源，表现出明显缺乏遗传多样性，这也许与它们独特而受限的栖息地有关。它们还具有广泛的杀死临床分离株痤疮丙酸杆菌的能力；噬菌体抗性并不普遍，但当检测到噬菌体抗性时，它似乎是由宿主基因组中染色体编码的免疫元件赋予的。我们相信，这些噬菌体具有许多使其成为痤疮噬菌体治疗理想候选物的特征。
