A Year of Infection in the Intensive Care Unit: Prospective Whole Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions and Novel Microbiota.
A Year of Infection in the Intensive Care Unit: Prospective Whole Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions and Novel Microbiota.
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DOI：
10.1371/journal.pgen.1005413
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发表时间：
2015-07
期刊：
影响因子：
4.5
通讯作者：
Salipante SJ
中科院分区：
文献类型：
--
作者：
Roach DJ;Burton JN;Lee C;Stackhouse B;Butler-Wu SM;Cookson BT;Shendure J;Salipante SJ
细菌全基因组测序有望成为临床微生物学中的一项颠覆性技术，但它尚未在临床背景下系统或全面地应用。在这里，在一年的过程中，我们进行了前瞻性收集和全基因组测序的几乎所有细菌分离株从三级保健医院的重症监护病房（ICU）。这一来自391名患者的1，229个细菌基因组的无偏见收集使临床病原体的几个特征的详细探索成为可能。一个相当大的比例的分离株确定为临床相关的对应于以前未描述的物种：12%的分离株分配的物种水平的分类，通过传统的方法，实际上有资格作为不同的，新的基因组种的基础上的基因组相似性。对收集的最常见病原体的泛基因组分析显示，泛基因组大小（1，420至20，432个基因）和基因发现率（每个测序分离株1至152个基因）存在显著差异。令人惊讶的是，尽管积极监测的病原体的潜在医院传播是罕见的，但8.7%的分离株属于基因组相关的克隆谱系，这些克隆谱系存在于多个患者中，通常具有重叠的入院时间，并且与62%的患者中的临床显著感染相关。多患者克隆谱系在新生儿监护室中特别明显，其中鉴定了7个独立的表皮葡萄球菌克隆谱系，包括5/9名新生儿中与菌血症相关的一个谱系。我们的研究突出了传统微生物学实践与全基因组测序提供的信息的关键差异，并促使微生物基因组测序进一步整合到常规临床护理中。细菌全基因组测序在微生物学研究中变得越来越普遍，但尽管其具有巨大的潜力，但尚未有意义地整合到临床护理中。在这里，我们从医院重症监护室前瞻性收集的几乎所有细菌分离株中生成了一整年的全基因组测序数据。我们的分析确定了住院患者中的新型微生物群，患者感染多种不相关的细菌物种谱系的高发生率，以及患者之间细菌隐性传播的可能性。我们的研究在提供影响医院最严重患者的细菌感染的广泛和公正的观点方面是前所未有的，并证明了在很长一段时间内可以从临床细菌分离株的全面基因组监测中了解到的信息程度。
Bacterial whole genome sequencing holds promise as a disruptive technology in clinical microbiology, but it has not yet been applied systematically or comprehensively within a clinical context. Here, over the course of one year, we performed prospective collection and whole genome sequencing of nearly all bacterial isolates obtained from a tertiary care hospital’s intensive care units (ICUs). This unbiased collection of 1,229 bacterial genomes from 391 patients enables detailed exploration of several features of clinical pathogens. A sizable fraction of isolates identified as clinically relevant corresponded to previously undescribed species: 12% of isolates assigned a species-level classification by conventional methods actually qualified as distinct, novel genomospecies on the basis of genomic similarity. Pan-genome analysis of the most frequently encountered pathogens in the collection revealed substantial variation in pan-genome size (1,420 to 20,432 genes) and the rate of gene discovery (1 to 152 genes per isolate sequenced). Surprisingly, although potential nosocomial transmission of actively surveilled pathogens was rare, 8.7% of isolates belonged to genomically related clonal lineages that were present among multiple patients, usually with overlapping hospital admissions, and were associated with clinically significant infection in 62% of patients from which they were recovered. Multi-patient clonal lineages were particularly evident in the neonatal care unit, where seven separate Staphylococcus epidermidis clonal lineages were identified, including one lineage associated with bacteremia in 5/9 neonates. Our study highlights key differences in the information made available by conventional microbiological practices versus whole genome sequencing, and motivates the further integration of microbial genome sequencing into routine clinical care. Bacterial whole genome sequencing is becoming increasingly common to microbiological research, but despite its great potential, has not yet been meaningfully integrated into clinical care. Here, we generated whole genome sequencing data from nearly all of the bacterial isolates prospectively collected from a hospital’s intensive care units over an entire year. Our analysis identifies novel microbiota in hospitalized patients, a high incidence of patient infection with multiple unrelated lineages of a bacterial species, and the possibility of cryptic transmission of bacteria among patients. Our study is unprecedented in providing a broad and unbiased view of bacterial infections that affect the hospital’s sickest patients, and demonstrates the extent of information that can be learned from comprehensive genomic surveillance of clinical bacterial isolates over an extended period of time.