Genetic factors related to the widespread dissemination of ST11 extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae strains within hospital.
Genetic factors related to the widespread dissemination of ST11 extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae strains within hospital.
复制标题
医院内ST11广泛耐药碳青霉烯酶肺炎克雷伯菌广泛传播的遗传因素
DOI：
10.1097/cm9.0000000000001101
复制
发表时间：
2020-11-05
影响因子：
6.1
通讯作者：
Gao ZC
中科院分区：
文献类型：
--
作者：
Li DX;Zhai Y;Zhang Z;Guo YT;Wang ZW;He ZL;Hu SN;Chen YS;Kang Y;Gao ZC
摘要背景产碳青霉烯酶肺炎克雷伯菌（CP-Kp）由于广泛耐药（XDR）表型而面临着独特的临床挑战，序列型（ST） 11是中国最主要的携带blakpc -2的CP-Kp克隆。本回顾性研究的目的是探讨XDR CP-Kp ST11菌株在中国某三级医院重症监护病房（ICU）传播成功的遗传因素。方法2014年5 - 12月共鉴定出6株ST11 XDR CP-Kp菌株，采用最低抑菌浓度、聚合酶链反应、焦磷酸测序等方法进行验证。采用单分子实时测序法对6株ST11 XDR CP-Kp、3株多药耐药（MDR）和4株敏感菌株进行测序。通过比较基因组学的综合结构和功能分析，鉴定XDR ST11 CP-Kp菌株的基因组特征。结果从住院患者分离的ST11 XDR携带blakpc -2的CP-Kp菌株在医院ICU中传播。在功能上，ST11 XDR CP-Kp菌株与MDR和易感菌株相比，与信息存储和加工相关的基因更为丰富，尤其是与转座子和噬菌体等移动遗传元件相关的基因。在结构上，这些ST11 XDR CP-Kp菌株独特基因组的11个大规模遗传区域被鉴定为MGEs，包括转座子、整合子、噬菌体、基因组岛以及整合和共轭元件。其中3个位于质粒上，8个位于染色体上；其中5株具有耐药基因，8株具有适应相关基因。值得注意的是，在所有6株ST11 XDR CP-Kp菌株中都发现了一个新的含有blakpc -2的ΔΔTn1721-blaKPC-2转座子，可能是由IS903D和ISKpn8从ΔTn1721-blaKPC-2转座和截断的。结论在ST11 XDR CP-Kp株中发现的特异性MGEs可能与克隆传播一起促成了其强大的适应性，从而促进了其在医院的广泛传播。
Supplemental Digital Content is available in the text Abstract Background Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital. Methods Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains. Results We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ΔΔTn1721-blaKPC-2 transposon, probably transposed and truncated from ΔTn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains. Conclusion Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.