Whole-Genome Sequencing of Human Clinical Klebsiella pneumoniae Isolates Reveals Misidentification and Misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae.
Whole-Genome Sequencing of Human Clinical Klebsiella pneumoniae Isolates Reveals Misidentification and Misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae.
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DOI：
10.1128/mspheredirect.00290-17
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发表时间：
2017-07
期刊：
影响因子：
4.8
通讯作者：
Olsen RJ
中科院分区：
文献类型：
--
作者：
Long SW;Linson SE;Ojeda Saavedra M;Cantu C;Davis JJ;Brettin T;Olsen RJ
肺炎克雷伯菌是一种严重的人类病原体，与多种抗生素耐药和高死亡率有关。水痘克雷伯菌和准肺炎克雷伯菌是密切相关的生物体，通常被认为是毒性较低的机会致病菌。我们使用大规模、全面、基于人群的菌株收集和全基因组测序来调查我们医院系统中由这些微生物引起的感染。我们发现，在常规临床微生物学诊断中，天花克雷伯菌和准肺炎克雷伯菌分离株经常被误诊为肺炎克雷伯菌，并经常引起类似肺炎克雷伯菌的严重危及生命的感染。由于这些基因赋予了对许多不同的β -内酰胺类抗生素的抗性，因此在痘克雷伯氏菌和准肺炎克雷伯氏菌株中存在KPC以及在一株痘克雷伯氏菌株中存在NDM-1金属β -内酰胺酶尤其令人担忧。在这三种克雷伯菌之间共享质粒以及同源重组的证据是引起额外关注的原因。肺炎克雷伯菌是对公共卫生的主要威胁，在世界范围内造成严重的发病率和死亡率。高度耐药菌株的出现尤其令人担忧。人们已经认识到肺炎克雷伯菌并将其分为三个不同的系统发育群：肺炎克雷伯菌、水痘克雷伯菌和准肺炎克雷伯菌。天花克雷伯菌和准肺炎克雷伯菌通常被描述为机会致病菌，它们对人类的毒力比肺炎克雷伯菌小。最近，我们对从人类感染中恢复的1777株产扩展谱β -内酰胺酶（ESBL）的肺炎克雷伯菌进行了基因组测序，发现28株与天花克雷伯菌和准肺炎克雷伯菌在系统发育上有亲缘关系。对从患者身上恢复的另外95株非产esbl肺炎克雷伯菌进行全基因组测序，发现12株准肺炎克雷伯菌。基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）分析初步鉴定所有患者分离株为肺炎克雷伯菌，这表明传统临床微生物实验室鉴定方法存在潜在缺陷。全基因组序列分析揭示了克雷伯菌物种间核心基因含量和质粒复制子的广泛共享。首次发现了猪克雷伯菌和准肺炎克雷伯菌均携带肺炎克雷伯菌碳青霉烯酶（KPC）基因，而另一株猪克雷伯菌携带新德里金属β -内酰胺酶1 （NDM-1）基因。根据住院死亡率和感染类型评估，天花克雷伯菌和准肺炎克雷伯菌感染的毒性并不低于肺炎克雷伯菌感染。我们还发现了同源重组的证据，在一个克雷伯氏菌菌株，以及一个新的克雷伯氏菌菌株，这挑战了目前的克雷伯氏菌分支之间的相互关系的理解。肺炎克雷伯菌是一种严重的人类病原体，与多种抗生素耐药和高死亡率有关。水痘克雷伯菌和准肺炎克雷伯菌是密切相关的生物体，通常被认为是毒性较低的机会致病菌。我们使用大规模、全面、基于人群的菌株收集和全基因组测序来调查我们医院系统中由这些微生物引起的感染。我们发现，在常规临床微生物学诊断中，天花克雷伯菌和准肺炎克雷伯菌分离株经常被误诊为肺炎克雷伯菌，并经常引起类似肺炎克雷伯菌的严重危及生命的感染。由于这些基因赋予了对许多不同的β -内酰胺类抗生素的抗性，因此在痘克雷伯氏菌和准肺炎克雷伯氏菌株中存在KPC以及在一株痘克雷伯氏菌株中存在NDM-1金属β -内酰胺酶尤其令人担忧。在这三种克雷伯菌之间共享质粒以及同源重组的证据是引起额外关注的原因。
Klebsiella pneumoniae is a serious human pathogen associated with resistance to multiple antibiotics and high mortality. K. variicola and K. quasipneumoniae are closely related organisms that are generally considered to be less-virulent opportunistic pathogens. We used a large, comprehensive, population-based strain collection and whole-genome sequencing to investigate infections caused by these organisms in our hospital system. We discovered that K. variicola and K. quasipneumoniae isolates are often misidentified as K. pneumoniae by routine clinical microbiology diagnostics and frequently cause severe life-threatening infections similar to K. pneumoniae. The presence of KPC in K. variicola and K. quasipneumoniae strains as well as NDM-1 metallo-beta-lactamase in one K. variicola strain is particularly concerning because these genes confer resistance to many different beta-lactam antibiotics. The sharing of plasmids, as well as evidence of homologous recombination, between these three species of Klebsiella is cause for additional concern. Klebsiella pneumoniae is a major threat to public health, causing significant morbidity and mortality worldwide. The emergence of highly drug-resistant strains is particularly concerning. There has been a recognition and division of Klebsiella pneumoniae into three distinct phylogenetic groups: Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. K. variicola and K. quasipneumoniae have often been described as opportunistic pathogens that have less virulence in humans than K. pneumoniae does. We recently sequenced the genomes of 1,777 extended-spectrum-beta-lactamase (ESBL)-producing K. pneumoniae isolates recovered from human infections and discovered that 28 strains were phylogenetically related to K. variicola and K. quasipneumoniae. Whole-genome sequencing of 95 additional non-ESBL-producing K. pneumoniae isolates recovered from patients found 12 K. quasipneumoniae strains. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis initially identified all patient isolates as K. pneumoniae, suggesting a potential pitfall in conventional clinical microbiology laboratory identification methods. Whole-genome sequence analysis revealed extensive sharing of core gene content and plasmid replicons among the Klebsiella species. For the first time, strains of both K. variicola and K. quasipneumoniae were found to carry the Klebsiella pneumoniae carbapenemase (KPC) gene, while another K. variicola strain was found to carry the New Delhi metallo-beta-lactamase 1 (NDM-1) gene. K. variicola and K. quasipneumoniae infections were not less virulent than K. pneumoniae infections, as assessed by in-hospital mortality and infection type. We also discovered evidence of homologous recombination in one K. variicola strain, as well as one strain from a novel Klebsiella species, which challenge the current understanding of interrelationships between clades of Klebsiella. IMPORTANCE Klebsiella pneumoniae is a serious human pathogen associated with resistance to multiple antibiotics and high mortality. K. variicola and K. quasipneumoniae are closely related organisms that are generally considered to be less-virulent opportunistic pathogens. We used a large, comprehensive, population-based strain collection and whole-genome sequencing to investigate infections caused by these organisms in our hospital system. We discovered that K. variicola and K. quasipneumoniae isolates are often misidentified as K. pneumoniae by routine clinical microbiology diagnostics and frequently cause severe life-threatening infections similar to K. pneumoniae. The presence of KPC in K. variicola and K. quasipneumoniae strains as well as NDM-1 metallo-beta-lactamase in one K. variicola strain is particularly concerning because these genes confer resistance to many different beta-lactam antibiotics. The sharing of plasmids, as well as evidence of homologous recombination, between these three species of Klebsiella is cause for additional concern.