文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

IMP碳青霉烯酶的兴起与全球传播(1996 - 2023年):一项基因组流行病学研究

The rise and global spread of IMP carbapenemases (1996-2023): a genomic epidemiology study.

作者信息

Vezina Ben, Morampalli Bhargava Reddy, Nguyen Hoai-An, Gomez-Simmonds Angela, Peleg Anton Y, Macesic Nenad

出版信息

medRxiv. 2025 May 26:2025.05.25.25328332. doi: 10.1101/2025.05.25.25328332.


DOI:10.1101/2025.05.25.25328332
PMID:40492084
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12148276/
Abstract

BACKGROUND: IMP carbapenemases confer extensive drug resistance and are increasingly noted worldwide. Despite this, little is known regarding the global epidemiology of IMP carbapenemases. METHODS: We comprehensively identified genes in all publicly available bacterial genomes, then systematically analysed the distribution of variants across species, lineages, plasmids and mobile elements, examining patterns over time, across geographic regions and by source. Structural analysis of IMP variants was performed. FINDINGS: 4,556 -containing genomes were identified from 1996-2023, including 52 variants across 93 bacterial species. Key variants ( , , , and ) achieved global endemicity, while and were regionally endemic in Southeast Asia and North America, respectively. dissemination was driven by horizontal gene transfer, facilitating inter-species spread. Proliferation of multidrug-resistant , and lineages led to local outbreaks. Dereplication removed 3,175/4,556 (69.9%) genomes, indicating that most -containing genomes were highly related. variants were associated with mobile genetic element combinations including class 1 integrons and insertion sequences (99.7%), aiding mobilisation into ≥52 plasmid clusters, predominantly IncHI2A, IncN, IncL/M and IncC. Genomes of environmental and animal origin accounted for 10.0% and 1.1% of the dataset, respectively. Evidence of cross-source transmission was limited, with most spillover occurring between genomes of human and environmental origin. Structural analysis revealed a conserved carbapenemase structure (mean lDDT 0.977), with convergent missense mutations at seven catalytically relevant sites. INTERPRETATION: Global analysis enabled us to historically reconstruct the emergence and variant-specific epidemiologies of carbapenemase genes. Intersecting mobile elements enabled genes to spread across multiple plasmids and bacterial genera, facilitating global and multi-source spread within a One Health framework. Additionally, convergent evolutionary patterns indicate that IMP variants may continue evolving, potentially evading novel beta-lactam antimicrobial agents. FUNDING: NHMRC EL1 (APP1176324) to N.M.; NHMRC PF (APP1117940) to A.Y.P.; NIH/NIAID R01AI175414 to A.G-S. RESEARCH IN CONTEXT PANEL: Despite being a major cause of carbapenem resistance in Gram negative infections, little is known about the global epidemiology of IMP carbapenemases. IMP carbapenemases are metallo-beta-lactamases that were first identified in 1991 and have evolved into 96 different IMP variants. On May 21 2025, we searched all published reports available in PubMed using the terms "'IMP' and 'carbapenemase' genomics NOT (Review[Publication Type]) NOT (Case Reports[Publication Type]) NOT PCR" with no language restrictions and no publication date restrictions. We identified 223 articles, 62 and 121 of which reported single species or a single study centre/country, respectively. Only 6 articles employed genomics to examine multi-species and multi-geographical isolates, though this was in the context of carbapenem resistance more broadly rather than IMP carbapenemases specifically. The most relevant study included 38 globally distributed genomes across four species and tracked seven blaIMP variants across mobile genetic elements. To our knowledge, this global characterisation provides the most comprehensive account of carbapenemase gene epidemiology. To analyse the global distribution and diversity of genes, we compiled all available public genome data resulting in a dataset of 4,646 genomes. This has allowed us to identify local, regional and international spread of variants and determine the contributions of clonal expansion, plasmid proliferation and co-localised mobile genetic elements. We demonstrated that key variants display global (IMP-1, IMP-4, IMP-7, IMP-8 and IMP-13) and regional (IMP-26 within Southeast Asia and IMP-27 within North America) endemicity and that these patterns have been previously unacknowledged, reframing the previous understanding that IMP carbapenemases were largely confined to the Asia-Pacific region. Our observation of convergent evolutionary patterns raise concern that IMP variants may continue to evolve, potentially evading new β-lactam antimicrobials. This analysis has revealed the under-recognised contribution IMP carbapenemases make to global carbapenem resistance. These findings provide the first comprehensive atlas of carbapenemase gene dissemination and underscore the silent global spread of IMP carbapenemases. We note the critical need for enhanced surveillance systems, particularly in low- and middle-income countries, that can detect complex plasmid-mediated and mobile genetic element-associated spread, as we noted with carbapenemase genes. Moreover, our analyses show that systematic sampling across human, animal, and environmental reservoirs is crucial to address the One Health dimensions of emerging antimicrobial resistance threats. The study provides a framework for future interventions aimed at tracking and stopping the spread of IMP carbapenemases and calls for co-ordinated, real-time public health responses to this growing challenge.

摘要

背景:IMP碳青霉烯酶可导致广泛耐药,在全球范围内日益受到关注。尽管如此,关于IMP碳青霉烯酶的全球流行病学情况仍知之甚少。 方法:我们全面鉴定了所有公开可用细菌基因组中的IMP基因,然后系统分析了各变体在物种、谱系、质粒和移动元件中的分布,研究了随时间、地理区域和来源的模式。对IMP变体进行了结构分析。 研究结果:从1996年至2023年共鉴定出4556个含IMP的基因组,包括93种细菌中的52种IMP变体。关键变体(IMP-1、IMP-4、IMP-7、IMP-8和IMP-13)在全球流行,而IMP-26和IMP-27分别在东南亚和北美区域流行。IMP的传播由水平基因转移驱动,促进了种间传播。多重耐药的肺炎克雷伯菌、大肠埃希菌和铜绿假单胞菌谱系的增殖导致了局部暴发。重复数据去除了4556个基因组中的3175个(69.9%),表明大多数含IMP的基因组高度相关。IMP变体与包括1类整合子和插入序列在内的移动遗传元件组合相关(99.7%),有助于其转移到≥52个质粒簇中,主要是IncHI2A、IncN、IncL/M和IncC。环境和动物源基因组分别占数据集的10.0%和1.1%。跨源传播的证据有限,大多数溢出发生在人类和环境源基因组之间。结构分析揭示了一种保守的碳青霉烯酶结构(平均lDDT为0.977),在七个催化相关位点存在趋同的错义突变。 解读:全球分析使我们能够从历史角度重建IMP碳青霉烯酶基因的出现及特定变体的流行病学情况。相互交叉的移动元件使IMP基因能够在多个质粒和细菌属中传播,促进了在“同一个健康”框架内的全球和多源传播。此外,趋同的进化模式表明IMP变体可能会继续进化,有可能逃避新型β-内酰胺类抗菌药物。 资助:澳大利亚国家卫生与医学研究委员会(NHMRC)给N.M.的EL1基金(APP1176324);NHMRC给A.Y.P.的项目基金(APP1117940);美国国立卫生研究院(NIH)/美国国立过敏和传染病研究所(NIAID)给A.G-S.的R01AI175414基金。 研究背景:尽管IMP碳青霉烯酶是革兰阴性菌感染中碳青霉烯耐药的主要原因,但对其全球流行病学情况知之甚少。IMP碳青霉烯酶是金属β-内酰胺酶,于1991年首次被鉴定,现已进化为96种不同的IMP变体。2025年5月21日,我们在PubMed上搜索了所有已发表的报告,使用检索词“‘IMP’和‘碳青霉烯酶’基因组学 NOT(综述[文献类型])NOT(病例报告[文献类型])NOT PCR”,无语言限制和出版日期限制。我们鉴定出223篇文章,其中62篇和121篇分别报告了单一物种或单一研究中心/国家。只有6篇文章采用基因组学方法研究多物种和多地理区域的分离株,不过这是在更广泛的碳青霉烯耐药背景下,而非专门针对IMP碳青霉烯酶。最相关的研究包括来自四个物种的38个全球分布的基因组,并追踪了七个blaIMP变体在移动遗传元件中的情况。据我们所知,这种全球特征描述提供了关于IMP碳青霉烯酶基因流行病学最全面的描述。为了分析IMP基因的全球分布和多样性,我们汇总了所有可用的公共基因组数据,得到了一个包含4646个基因组的数据集。这使我们能够确定IMP变体的本地、区域和国际传播情况,并确定克隆扩增、质粒增殖和共定位移动遗传元件的作用。我们证明关键的IMP变体呈现全球(IMP-1、IMP-4、IMP-7、IMP-8和IMP-13)和区域(东南亚的IMP-26和北美的IMP-27)流行情况,且这些模式此前未被认识到,这重塑了之前认为IMP碳青霉烯酶主要局限于亚太地区的认识。我们对趋同进化模式的观察引发了担忧,即IMP变体可能会继续进化,有可能逃避新的β-内酰胺类抗菌药物。该分析揭示了IMP碳青霉烯酶对全球碳青霉烯耐药性的贡献未得到充分认识。这些发现提供了第一份IMP碳青霉烯酶基因传播的综合图谱,并强调了IMP碳青霉烯酶在全球范围内的隐性传播。我们指出迫切需要加强监测系统,特别是在低收入和中等收入国家,该系统能够检测复杂的质粒介导和移动遗传元件相关的传播,就像我们在IMP碳青霉烯酶基因方面所指出的那样。此外,我们的分析表明,对人类、动物和环境宿主进行系统采样对于应对新出现的抗菌药物耐药性威胁的“同一个健康”层面至关重要。该研究为未来旨在追踪和阻止IMP碳青霉烯酶传播的干预措施提供了框架,并呼吁针对这一日益严峻的挑战采取协调一致的实时公共卫生应对措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/8a5bdc734fc5/nihpp-2025.05.25.25328332v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/b6c0edf18ace/nihpp-2025.05.25.25328332v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/aead7be5c2ee/nihpp-2025.05.25.25328332v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/b8dc226ab678/nihpp-2025.05.25.25328332v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/2421723208df/nihpp-2025.05.25.25328332v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/12fa0aeed26e/nihpp-2025.05.25.25328332v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/941f72593880/nihpp-2025.05.25.25328332v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/8a5bdc734fc5/nihpp-2025.05.25.25328332v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/b6c0edf18ace/nihpp-2025.05.25.25328332v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/aead7be5c2ee/nihpp-2025.05.25.25328332v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/b8dc226ab678/nihpp-2025.05.25.25328332v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/2421723208df/nihpp-2025.05.25.25328332v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/12fa0aeed26e/nihpp-2025.05.25.25328332v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/941f72593880/nihpp-2025.05.25.25328332v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e98e/12148276/8a5bdc734fc5/nihpp-2025.05.25.25328332v1-f0007.jpg

相似文献

[1]
The rise and global spread of IMP carbapenemases (1996-2023): a genomic epidemiology study.

medRxiv. 2025-5-26

[2]
Tracing the evolutionary trajectory of the IncP-2 plasmid co-harboring and : an outbreak of co-producing IMP-45 and VIM-1 carbapenemases in China.

Front Cell Infect Microbiol. 2025-6-19

[3]
Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates.

BMC Infect Dis. 2022-7-7

[4]
Molecular epidemiology of extended-spectrum beta-lactamase-producing bloodstream infections from Aberdeen, Scotland, and their comparison to isolates from England.

Microb Genom. 2025-6

[5]
Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

Lancet Microbe. 2025-7-16

[6]
Enhancement of -carrying plasmid transfer in by hospital wastewater: a transcriptomic study.

Front Microbiol. 2025-7-28

[7]
Import of global high-risk clones is the primary driver of carbapenemase-producing in Norway.

J Med Microbiol. 2025-1

[8]
Genomic epidemiology and resistome dynamics of species in a Portuguese Open Air Laboratory: the emergence of the FRI-8 carbapenemase.

Front Microbiol. 2025-7-31

[9]
Distinct adaptation and epidemiological success of different genotypes within serovar Dublin.

Elife. 2025-6-25

[10]
Carbapenemases producing gram-negative bacteria surveillance in Latin America and the caribbean: a retrospective observational study from 2015 to 2020.

Lancet Reg Health Am. 2025-7-15

本文引用的文献

[1]
The WHO Bacterial Priority Pathogens List 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance.

Lancet Infect Dis. 2025-4-11

[2]
Epidemiology and outcomes associated with MBL-producing Enterobacterales: A systematic literature review.

Int J Antimicrob Agents. 2025-4

[3]
Mechanisms of bla dissemination across diverse carbapenem-resistant clinical isolates.

J Glob Antimicrob Resist. 2025-3

[4]
Integrons are key players in the spread of beta-lactamase-encoding genes.

Int J Antimicrob Agents. 2025-3

[5]
Mobilization of an ICEclc-Like Element as a Potential Mechanism for the Spread of IMP-13 Carbapenemase in Pseudomonas aeruginosa.

J Glob Antimicrob Resist. 2025-3

[6]
Global genomic epidemiology of carbapenemase-associated integrons.

Microb Genom. 2024-12

[7]
Diversity, functional classification and genotyping of SHV β-lactamases in .

Microb Genom. 2024-10

[8]
Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050.

Lancet. 2024-9-28

[9]
Integrated Analysis of Patient Networks and Plasmid Genomes to Investigate a Regional, Multispecies Outbreak of Carbapenemase-Producing Enterobacterales Carrying Both blaIMP and mcr-9 Genes.

J Infect Dis. 2024-7-25

[10]
The outbreak of multispecies carbapenemase-producing Enterobacterales associated with pediatric ward sinks: IncM1 plasmids act as vehicles for cross-species transmission.

Am J Infect Control. 2024-7

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索