Insertion sequence-driven diversification creates a globally dispersed emerging multiresistant subspecies of E. faecium.
Insertion sequence-driven diversification creates a globally dispersed emerging multiresistant subspecies of E. faecium.
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DOI：
10.1371/journal.ppat.0030007
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发表时间：
2007-01
期刊：
影响因子：
6.7
通讯作者：
Bonten MJ
中科院分区：
文献类型：
--
作者：
Leavis HL;Willems RJ;van Wamel WJ;Schuren FH;Caspers MP;Bonten MJ
屎肠球菌是人类和动物的普遍定植者，在过去的15年中，屎肠球菌已经从无毒的细菌进化为美国重症监护病房患者中第三大最常见的医院内病原体。E.屎肠球菌结合了多药耐药性和水平耐药基因转移到甚至更多致病细菌的潜力。目前对E.由于缺乏完整注释的基因组序列，基因组研究受到阻碍。为了进一步阐明其进化，我们使用了一个混合的全基因组芯片和杂交97 E。来自不同背景（医院爆发（n = 18）、记录的感染（n = 34）和住院患者的无症状携带（n = 15）以及健康人（n = 15）和动物（n = 21））的屎肠分离物。贝叶斯后验概率（PP = 1.0）的支持下，一个特定的分支包含所有爆发相关的菌株和63%的临床分离株被确定。对437个进化枝特异性插入片段中的146个进行测序，发现了移动的元件（n = 74），包括插入序列（IS）元件（n = 42）、噬菌体基因（n = 6）和质粒序列（n = 26）、假设（n = 58）和膜蛋白（n = 10）以及抗生素抗性（n = 9）和调节基因（n = 11），主要位于未完成的E.屎肠DO基因组。分裂分解分析，不同的鸟嘌呤胞嘧啶含量，和异常的密码子适应指数都支持收购这些基因通过水平基因转移与IS16作为预测的最突出的插入（98%敏感，100%特异性）。这些发现表明IS元件的获得促进了不同E的生态位适应。faecium亚群通过增加其基因组可塑性。支持基因组可塑性的增加，较高的多样性指数（脉冲场凝胶电泳和多位点序列分型的平均遗传相似性的比率）的分支特异性菌株。有趣的是，先前描述的基于多基因座序列分型的克隆复合物17在很大程度上与该进化枝重叠。目前的数据表明，E. faecium，自1990年以来观察到，代表了一个亚种的进化，可能比其他E.粪便分离株的限制，医院环境。全基因组测序已成为研究细菌基因组内容的工具。然而，细菌种群内存在巨大的多样性，并且多个基因组的注释是昂贵且复杂的。为了研究细菌物种内的多样性和同源性，比较基因组杂交是一种有吸引力的替代方法，可以提供区分细菌亚群的因素（基因）的基本见解。屎肠球菌是一种世界范围内出现的医院病原体，通常对多种抗生素具有耐药性，会导致免疫功能低下患者感染。利用比较基因组杂交技术，对97株E.屎肠球菌（E. faecium）是从世界各地不同的流行病学小生境中分离的屎肠球菌（E. faecium）的一个亚群。确定了与侵入性感染和医院爆发有关的屎肠菌株。约13%的E. faecium pangenome对该亚群具有高度特异性，基于系统发育聚类，应将其视为一个亚种。我们假设，广泛的变化，在特定的功能基因和高流行率的移动的元素，主要是插入序列元素，有助于成功的遗传子集在医院环境中与其他肠球菌的竞争，创造一个新的全球分散的医院内亚种。这些发现充分证实了以前基于多位点序列分型的系统发育研究，也揭示了E。粪菌，克隆复合体17。克隆复合物17的特异性基因的鉴定是阐明这种新出现的医院病原体如何全球传播和适应医院环境的第一步。
Enterococcus faecium, an ubiquous colonizer of humans and animals, has evolved in the last 15 years from an avirulent commensal to the third most frequently isolated nosocomial pathogen among intensive care unit patients in the United States. E. faecium combines multidrug resistance with the potential of horizontal resistance gene transfer to even more pathogenic bacteria. Little is known about the evolution and virulence of E. faecium, and genomic studies are hampered by the absence of a completely annotated genome sequence. To further unravel its evolution, we used a mixed whole-genome microarray and hybridized 97 E. faecium isolates from different backgrounds (hospital outbreaks (n = 18), documented infections (n = 34) and asymptomatic carriage of hospitalized patients (n = 15), and healthy persons (n = 15) and animals (n = 21)). Supported by Bayesian posterior probabilities (PP = 1.0), a specific clade containing all outbreak-associated strains and 63% of clinical isolates was identified. Sequencing of 146 of 437 clade-specific inserts revealed mobile elements (n = 74), including insertion sequence (IS) elements (n = 42), phage genes (n = 6) and plasmid sequences (n = 26), hypothetical (n = 58) and membrane proteins (n = 10), and antibiotic resistance (n = 9) and regulatory genes (n = 11), mainly located on two contigs of the unfinished E. faecium DO genome. Split decomposition analysis, varying guanine cytosine content, and aberrant codon adaptation indices all supported acquisition of these genes through horizontal gene transfer with IS16 as the predicted most prominent insert (98% sensitive, 100% specific). These findings suggest that acquisition of IS elements has facilitated niche adaptation of a distinct E. faecium subpopulation by increasing its genome plasticity. Increased genome plasticity was supported by higher diversity indices (ratio of average genetic similarities of pulsed-field gel electrophoresis and multi locus sequence typing) for clade-specific isolates. Interestingly, the previously described multi locus sequence typing–based clonal complex 17 largely overlapped with this clade. The present data imply that the global emergence of E. faecium, as observed since 1990, represents the evolution of a subspecies with a presumably better adaptation than other E. faecium isolates to the constraints of a hospital environment. Whole-genome sequencing has become instrumental in investigating the genome contents of bacteria. However, there is enormous diversity within bacterial populations, and annotation of multiple genomes is costly and elaborate. For investigating diversity and phylogeny within bacterial species, comparative genomic hybridization is an attractive alternative that may provide fundamental insights into the factors (genes) distinguishing bacterial subpopulations. Enterococcus faecium, a worldwide emerging nosocomial pathogen usually resistant to multiple antibiotics, causes infections in immunocompromised patients. Using comparative genomic hybridization of 97 E. faecium strains isolated from different epidemiological niches worldwide, a subpopulation of E. faecium strains was identified that was associated with invasive infections and hospital outbreaks. Approximately 13% of the E. faecium pangenome was highly specific for this subpopulation, and, based on phylogenetic clustering, it should be considered a subspecies. We hypothesize that extensive variation within specific functional genes and high prevalence of mobile elements, mostly insertion sequence elements, contributed to the success of this genetic subset in its competition with other enterococci in hospital settings, creating a novel globally dispersed nosocomial subspecies. These findings fully confirmed previous phylogenetic studies based on multi locus sequence typing that had also revealed a genetic subset of E. faecium, clonal complex 17. Identification of genes specific for clonal complex 17 is a first step in elucidating how global spread and adaptation to the hospital environment of this emerging nosocomial pathogen has occurred.
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影响因子：
2.8
作者：
Dahl, KH;Lundblad, EW;Sundsfjord, A
通讯作者：
Sundsfjord, A
影响因子：
4.9
作者：
Fines, M;Perichon, B;Courvalin, P
通讯作者：
Courvalin, P
DOI：
10.1073/pnas.0503252102
发表时间：
2005-11-01
影响因子：
11.1
作者：
Champion, OL;Gaunt, MW;Wren, BW
通讯作者：
Wren, BW
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
6.4
作者：
Bonten, MJM;Hayden, MK;Weinstein, RA
通讯作者：
Weinstein, RA