Li Dai-Xi, Zhai Yao, Zhang Zhao, Guo Ya-Tao, Wang Zhan-Wei, He Zi-Long, Hu Song-Nian, Chen Yu-Sheng, Kang Yu, Gao Zhan-Cheng
Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
University of Technology Sydney, Ultimo, NSW 2007, Australia.
Chin Med J (Engl). 2020 Nov 5;133(21):2573-2585. doi: 10.1097/CM9.0000000000001101.
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.
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.
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.
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.
产碳青霉烯酶肺炎克雷伯菌（CP-Kp）因其广泛耐药（XDR）表型带来了独特的临床挑战，序列型（ST）11是中国携带blaKPC-2的CP-Kp最主要的克隆株。本回顾性研究的目的是探索在中国一家三级医院重症监护病房（ICU）中传播的XDR CP-Kp ST11菌株成功传播的相关遗传因素。
2014年5月至12月间鉴定出6株ST11 XDR CP-Kp菌株，并通过最低抑菌浓度检测、聚合酶链反应和焦磷酸测序进行验证。使用单分子实时方法对这6株ST11 XDR CP-Kp菌株以及3株多重耐药（MDR）菌株和4株敏感菌株进行测序。基于比较基因组学进行全面的结构和功能分析，以鉴定XDR ST11 CP-Kp菌株的基因组特征。
我们发现从住院患者中分离出的携带blaKPC-2的ST11 XDR CP-Kp菌株在医院的ICU中传播。在功能上，ST11 XDR CP-Kp菌株中与信息存储和处理相关的基因比MDR菌株和敏感菌株更为丰富，尤其是与转座子和噬菌体等可移动遗传元件（MGE）相关的基因。在结构上，这些ST11 XDR CP-Kp菌株中被视为独特基因组的11个大规模遗传区域被鉴定为MGE，包括转座子、整合子、噬菌体、基因组岛以及整合和接合元件。其中3个位于质粒上，8个位于染色体上；5个带有抗菌抗性基因，8个带有适应性相关基因。值得注意的是，在所有6株ST11 XDR CP-Kp菌株中均鉴定出一种新的携带blaKPC-2的ΔΔTn1721-blaKPC-2转座子，可能是由IS903D和ISKpn8从ΔTn1721-blaKPC-2转座并截断而来。
我们的研究结果表明，与克隆传播一起，在ST11 XDR CP-Kp菌株中独特鉴定出的MGE可能有助于其强大的适应性，这促进了它们在医院中的广泛传播。
