Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307.
Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307.
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DOI：
10.1128/mbio.00489-17
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发表时间：
2017-05-16
期刊：
影响因子：
6.4
通讯作者：
Musser JM
中科院分区：
文献类型：
--
作者：
Long SW;Olsen RJ;Eagar TN;Beres SB;Zhao P;Davis JJ;Brettin T;Xia F;Musser JM
肺炎克雷伯氏菌是导致高发病率和死亡率的主要人类病原体。对多种抗菌药物耐药菌株的出现和传播以及有记录的大规模院内暴发尤其令人担忧。为了开发肺炎克雷伯菌的新治疗策略，必须了解引起人类感染的菌株的群体基因组结构。为了解决这一知识缺口，我们对2011年9月至2015年5月期间在休斯顿卫理公会医院系统的2,000张病床中培养的1，777株产超广谱β-内酰胺酶肺炎克雷伯菌菌株的基因组进行了测序，代表了一个全面的，基于人群的菌株样本。在很大程度上未表征的克隆组307（CG 307）的菌株引起更多的感染比那些充分研究的流行病CG 258。菌株的基因含量差异很大，有大量的小质粒和非常大的质粒，通常含有抗菌素耐药基因。一些患者随着时间的推移培养出多种菌株，感染了遗传上不同的克隆。我们鉴定了15株表达新德里金属β-内酰胺酶1（NDM-1）的菌株，该酶对几乎所有β-内酰胺抗生素都具有广泛的耐药性。对10株具有不同遗传多样性的菌株的转录组测序分析表明，每株菌株的总体转录组是独特的，并且高度可变。实验小鼠感染提供了新的信息宿主-病原体相互作用的免疫学参数。我们利用大数据集开发了基于全基因组序列的分类器，可以准确预测16种抗生素中12种的临床耐药性。我们的结论是，分析大型，全面，基于人群的菌株样本可以帮助了解这些生物的分子多样性，并有助于加强转化研究。肺炎克雷伯氏菌引起的人类感染越来越难以治疗，因为许多菌株对多种抗生素具有耐药性。克隆群258（CG 258）微生物已在全球卫生保健环境中引起暴发。使用一个全面的基于人群的产超广谱β-内酰胺酶（ESBL）肺炎克雷伯菌菌株的样本，我们发现一个相对罕见的克隆型，CG 307，导致我们的患者中的多种产ESBL肺炎克雷伯菌感染。我们发现，CG 307菌株在休斯顿已经大量存在多年。如通过实验小鼠感染所评估的，CG 307菌株与大流行CG 258菌株一样毒力。我们的研究结果可能预示着一个特别成功的耐药肺炎克雷伯菌克隆群的出现。
Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae.