Regulatory role of ISEcp1 and spacer sequences in blaCTX-M–mediated cephalosporin resistance in Shigella

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance Pub Date : 2025-06-20 DOI:10.1016/j.jgar.2025.06.005

Hui Zhang , Shengkun He , Xiaoying Pang , Xi He , Xuechun Liu , Shaofu Qiu , Chaojie Yang , Hongbin Song

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引用次数: 0

Abstract

Background

Extended-spectrum β-lactamases, especially CTX-M enzymes, play a critical role in cephalosporin resistance in several bacterial species. The ISEcp1 insertion sequence, a mobile genetic element, regulates the high expression and horizontal transfer of the bla_CTX-M gene. Diverse types of spacer regions exist, the length of which varies across the different types of bla_CTX-M genes and their upstream ISEcp1 elements. In this study, we aimed to investigate the distribution and role of ISEcp1 and different length spacers in antibiotic-resistant Shigella.

Methods

We selected 1393 cephalosporin-resistant Shigella strains isolated from China between 2004 and 2016 to analyse the distribution of ISEcp1 and spacers using polymerase chain reaction and sequencing. To functionally evaluate the role of these elements, we designed different combinations of ISEcp1, spacer sequences, and bla_CTX-M gene fragments to generate and express recombinant plasmids containing these fragments in Escherichia coli. We then assessed the cephalosporin resistance phenotype of recombinant clones using the E-TEST method.

Results

The carriage rate of ISEcp1 in cephalosporin-resistant Shigella was 90.09%, with an ISEcp1-CTX-M element carriage rate of 67.19%, and was significantly higher in the bla_CTX-M-9 group than that in the bla_CTX-M-1 group. Moreover, E. coli strains containing different combinations exhibited varying bacterial resistance to β-lactam antibiotics, indicating the regulatory role of ISEcp1 and spacers.

Conclusions

Our results demonstrate that the configuration of ISEcp1, spacer sequences, and bla_CTX-M in plasmids fosters a robust resistance phenotype against various cephalosporins, providing new insights into antimicrobial resistance mechanisms and an important basis for developing novel anti-resistance drugs.

Abstract Image

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ISEcp1和间隔序列在blactx - m介导的志贺菌头孢菌素耐药中的调控作用

背景：广谱β-内酰胺酶，特别是CTX-M酶，在几种细菌的头孢菌素耐药中起关键作用。ISEcp1插入序列是一个可移动的遗传元件，调控blaCTX-M基因的高表达和水平转移。存在不同类型的间隔区，其长度在不同类型的blaCTX-M基因及其上游ISEcp1元件中有所不同。在这项研究中，我们旨在研究ISEcp1和不同长度间隔物在耐药志贺菌中的分布和作用。方法：选取2004 - 2016年中国分离的1393株耐头孢菌素志贺菌，采用PCR和测序方法分析ISEcp1和间隔序列的分布。为了从功能上评估这些元件的作用，我们设计了ISEcp1、间隔序列和blaCTX-M基因片段的不同组合，在大肠杆菌中产生并表达含有这些片段的重组质粒。然后，我们使用E-TEST方法评估重组克隆的头孢菌素耐药表型。结果：ISEcp1在耐头孢菌素志贺菌中的携带率为90.09%，ISEcp1- ctx - m元件携带率为67.19%，且blaCTX-M-9组明显高于blaCTX-M-1组。此外，含有不同组合的大肠杆菌菌株对β-内酰胺类抗生素表现出不同的细菌耐药性，表明ISEcp1和间隔物的调节作用。结论：我们的研究结果表明，质粒中ISEcp1、间隔序列和blaCTX-M的配置促进了对多种头孢菌素的强劲耐药表型，为抗生素耐药机制的研究提供了新的见解，并为开发新的耐药药物提供了重要基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY

CiteScore

8.70

自引率

2.20%

发文量

285

审稿时长

34 weeks

期刊介绍： The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.