Study on the epidemiology and genetic background of Enterobacteriaceae co-harboring blaKPC and mcr genes based on NCBI database

doi:10.12211/2096-8280.2025-079

Abstract

Abstract:

(Objective) To systematically study the global distribution characteristics of Enterobacteriaceae harboring carbapenem resistance gene (bla_KPC) and polymyxin resistance gene (mcr) based on NCBI database, as well as the genetic background of these resistance genes, providing a reference for disease prevention and control. (Methods) Whole-genome data of bacteria harboring bla_KPC and mcr genes were downloaded from the NCBI database. Different subtypes of bla_KPC and mcr genes in the strains were analyzed and identified. By annotating bacterial plasmids and identifying replicon types, the presence of these resistance genes in specific plasmids was revealed. The upstream and downstream genetic structures of the bla_KPC and mcr genes were also analyzed. (Results) The bacteria co-harboring bla_KPC and mcr genes were primarily from the Enterobacteriaceae family, with the main distribution in the United States, the United Kingdom, and China. The diversity of bacterial genera harboring both bla_KPC and mcr genes increased from 2012 to 2018. The dominant genotype combinations were bla_KPC-2+mcr-9.1 and bla_KPC-3+mcr-9.1. In this study, the genotype bla_KPC-2+mcr-9.1+mcr-9.2 was found in various STs of Escherichia coli (58, 46.03%). Genetic environment analysis showed that bla_KPC is mainly located on the pKPC-CAV1193 plasmid, with a significant identification of the tnpR-tnpA-ISkpn7-bla_KPC-ISkpn6 (Tn4401b) transposon structure. mcr-9.1 is mainly located on the IncHI2 (2A) plasmid, with conserved upstream and downstream genetic structures, the core structure being rcnR-rcnA-pcoE-pcoS-IS903B-mcr-9.1-wbuC-IS26. (Conclusion) Strains co-harboring the bla_KPC and mcr genes show significant geographic distribution differences. Special attention should be given to the potential for transmission of specific ST types of Escherichia coli (such as ST167 and ST10) and their changes in clinical environments. The resistance genes bla_KPC and mcr are transmitted through specific plasmids, pKPC-CAV1193 and IncHI2 (2A), respectively, and spread via transposons and other mobile genetic elements, greatly increasing the risk of resistance transmission, which warrants urgent attention.

Key words: bla_KPC, mcr, Enterobacteriaceae, plasmid, transposon, MGEs

摘要：

（目的）利用生物信息学技术，系统研究NCBI数据库中共同携带碳青霉烯类耐药基因（bla_KPC）和多黏菌素耐药基因（mcr）肠杆菌科细菌流行分布特征，及耐药基因遗传背景，为共耐药菌株的感染防控提供参考依据。（方法）从NCBI数据库中下载了携带bla_KPC和mcr基因的细菌全基因组数据，分析并鉴定了菌株中bla_KPC和mcr的不同亚型。通过对细菌质粒的注释和复制子类型的鉴定，揭示这两种耐药基因在特定质粒中的存在情况，并分析了bla_KPC和mcr基因的上下游遗传结构。（结果）共同携带bla_KPC和mcr基因细菌主要为肠杆菌科细菌，且以美国、英国和中国为主要分布国家。共同携带bla_KPC和mcr基因菌株菌属分布多样性在2012年至2018年有所增加。bla_KPC-2+mcr-9.1以及bla_KPC-3+mcr-9.1为优势基因型组合，且本研究中bla_KPC-2+mcr-9.1+mcr-9.2基因型分布于多种STs的大肠埃希氏菌（58，46.03%）。遗传环境分析表明：bla_KPC主要位于pKPC-CAV1193质粒，并大量鉴定到tnpR-tnpA-ISkpn7-bla_KPC-ISkpn6（Tn4401b）这一转座子结构；mcr-9.1主要位于IncHI2（2A）质粒中，且上下游遗传结构保守，核心结构为rcnR-rcnA-pcoE-pcoS-IS903B-mcr-9.1-wbuC-IS26。（结论）共同携带bla_KPC和mcr基因菌株有显著的地域分布差异；应特别关注特定ST型大肠埃希氏菌（如ST167和ST10）在传播中的潜力，及在临床环境中的变化。耐药基因bla_KPC和mcr分别主要通过pKPC-CAV1193及IncHI2（2A）质粒介导传播，并通过转座子等可移动遗传元件进行扩散，极大增加了耐药性传播的风险，应引起高度重视。

关键词: bla_KPC, mcr, 肠杆菌科细菌, 质粒, 转座子, 可移动遗传元件

CLC Number:

R378

FU Jing-jing, HU Xiao-feng, WANG Bo-qian, HU Gui-fang, HE Ya-qing. Study on the epidemiology and genetic background of Enterobacteriaceae co-harboring bla_KPC and mcr genes based on NCBI database[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2025-079.

付晶晶, 胡晓丰, 王博千, 胡贵方, 何雅青. 基于NCBI数据库的共同携带bla_KPC和mcr基因肠杆菌科细菌流行现状和耐药基因遗传背景研究[J]. 合成生物学, DOI: 10.12211/2096-8280.2025-079.

Figures/Tables 6

Fig. 1 Temporal distribution of 663 strains co-harboring blaKPC and mcr genes.

Fig. 2 (a) Radar chart of the distribution of resistant genes blaKPC and mcr. (b) Source distribution of strains co-harboring blaKPC and mcr genes.

Table 1 National distribution of 663 strains co-harboring blaKPC and mcr genes

国家	数量（株）	构成比（%）
美国	285	42.99
英国	117	17.65
中国	75	11.31
新加坡	63	9.50
加拿大	49	7.39
巴西	12	1.81
德国	10	1.51
其他	39	5.88
未知	13	1.96

Fig. 3 Genotype distribution statistics of strain co-harboring blaKPC and mcr genes: upset-venn diagram.(Note: blaKPC (others) refers to blaKPC-18, blaKPC-5, blaKPC-6, and blaKPC-8 found in this dataset, which are less frequent (fewer than 10 occurrences), and are therefore grouped together as blaKPC (others). The same applies to mcr (others). The number in the bottom-left corner represents the frequency with which different subtypes of resistant genes appear as the sole element in genotype combinations.)

Fig.4 The MLST minimum spanning tree of Klebsiella pneumoniae and Escherichia coli constructed based on GrapeTree software(a) Minimum spanning tree analysis of 92 Klebsiella pneumoniae strains. (b) Minimum spanning tree analysis of 120 Escherichia coli strains.Each circle (node) corresponds to an ST identified by a specific number. The color of the circle represents different genotype combinations, and the size of the circle is proportional to the number of isolated strains (genomes). The numbers in square brackets indicate the number of isolates for each genotype combination.

Fig. 5 Genetic context of blaKPC and mcr genes.(The colored arrows represent open reading frames. Red, green, and blue arrows represent antibiotic resistance genes, mobile genetic elements, and heavy metal resistance genes, respectively. Other annotated and unannotated genes are displayed in orange and gray. Gray shading indicates genetic regions showing sequence homology between different segments.)

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