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头孢他啶-阿维巴坦耐药革兰氏阴性菌的流行病学特征及耐药机制 Review
徐婷婷, 郭育奇, 姬扬, 王保红, 周凯
《工程（英文）》 2022年 第11卷 第4期 页码 138-145 doi: 10.1016/j.eng.2020.11.004
细菌的碳青霉烯耐药性是全球公共健康面临的一个重大挑战，由碳青霉烯耐药菌（CRO）引起的临床感染通常有很高的发病率和死亡率。然而，这种药物在临床使用后不久，细菌的耐药性就已经出现，并且呈上升趋势。了解细菌对CAZ-AVI 的耐药机制，对于指导开发新型治疗方法、帮助预测潜在的耐药机制至关重要。本文旨在系统总结CAZ-AVI 耐药菌株的流行病学发展过程和最近发现的CAZ-AVI 耐药机制；将重点关注β-内酰胺酶突变体的产生、β-内酰胺酶高表达、细胞表面通透性降低以及药物外排泵的过表达短时间内多种CAZ-AVI耐药机制的产生，强调了临床合理用药的重要性以及监测CAZ-AVI 耐药性病原体的必要性。
细菌耐药性威胁人类健康 Editorial
沈建忠, Timothy R. Walsh
《工程（英文）》 2022年 第15卷 第8期 页码 1-2 doi: 10.1016/j.eng.2022.06.003
越南广平和顺化两省猪场分离副猪嗜血杆菌的抗生素耐药表型和耐药基因之间的相关性研究 Article
Chao Nguyen Van, 张丽君, Tam Vu Thi Thanh, Hung Pham Hoang Son, Tuan Tran Ngoc, 黄琦, 周锐
《工程（英文）》 2020年 第6卷 第1期 页码 40-48 doi: 10.1016/j.eng.2019.10.014
关键词： 副猪嗜血杆菌，抗药性，耐药基因，越南
夏照帆,吕开阳,汤陈琪,李骏强
《中国工程科学》 2017年 第19卷 第2期 页码 106-111 doi: 10.15302/J-SSCAE-2017.02.018
细菌耐药危机日趋严峻，已经成为全球范围内的重大公共安全问题，严重危害人类、动物的健康和生态环境。本文总结了我国各领域细菌耐药问题的现状，分析了加剧细菌耐药性的直接原因，揭示了细菌耐药问题对国民健康、食品安全、生态环境、经济发展等可能造成的危害，整理了我国目前开展的防控行动以及取得的主要成果，最后针对我国细菌耐药防控在耐药监测、抗生素监管、危害风险评估、人才队伍建设等方面的不足，提出了多领域合作、多部门联防联控的细菌耐药防控策略。
猪链球菌中发现可介导链阳菌素A、截短侧耳素类以及林可酰胺类药物耐药的新型耐药基因 srpA Article
张朝阳, 刘璐, 张朋, 崔箐坡, 秦晓霞, 马立超, 韩坤, 王战辉, 王少林, 丁双阳, 沈张奇
《工程（英文）》 2022年 第9卷 第2期 页码 85-94 doi: 10.1016/j.eng.2020.12.015
细菌耐药性问题毫无疑问是全球最大的健康威胁之一。耐甲氧西林的金黄色葡萄球菌、耐万古霉素的屎肠球菌和耐β-内酰胺的肺炎链球菌等多重耐药革兰氏阳性菌的出现，严重限制了临床可用的抗菌药物。截短侧耳素类、恶唑烷酮类以及链阳霉素类等许多靶向核糖体的抗菌药物，有望成为治疗这些多重耐药病原体的替代选择。本研究中，我们通过比较基因组学，在截短侧耳素类耐药猪链球菌中发现了一个新型耐药基因srpA。功能克隆试验显示该基因可以介导猪链球菌和金黄色葡萄球菌等对截短侧耳素类、林可酰胺类和链阳菌素A类抗菌药物的交叉耐药性。进一步研究发现SrpA 中loop 区的氨基酸突变或缺失将不同程度地影响细菌的耐药性，证实该结构域对SrpA 功能至关重要。这些研究结果阐明了SrpA介导耐药的分子机制。
微生物耐药性在人与动物间的传播——我们为什么需要知道更多？ Views & Comments
Julian Parkhill
《工程（英文）》 2022年 第15卷 第8期 页码 11-12 doi: 10.1016/j.eng.2022.04.007
基于同一健康策略探究老挝人、动物和环境中多黏菌素耐药性的传播特征 Article
周宇晴, Refath Farzana, Somsavanh Sihalath, Sayaphet Rattanavong, Manivanh Vongsouvath, Mayfong Mayxay, Kirsty Sands, Paul N. Newton, David A.B. Dance, Brekhna Hassan, Timothy R. Walsh
《工程（英文）》 2022年 第15卷 第8期 页码 45-56 doi: 10.1016/j.eng.2022.01.013
This study was designed to investigate the molecular epidemiology of mobile colistin resistance (mcr) using a "One-Health" approach in Laos and to predict whether any dominant plasmid backbone and/or strain type influences the dissemination of mcr. We collected 673 samples from humans (rectal normal flora), poultry, and the environment (water, flies, birds, etc.) in Vientiane, Lao People's Democratic Republic (Laos), from May to September 2018. A total of 238 Escherichia coli (E. coli) isolated from nonduplicative samples, consisting of 98 MCR-positive E. coli (MCRPEC) ("mcr" denotes the gene encoding mobile colistin resistance, and "MCR" denotes the subsequent protein encoded by mcr) and 140 MCRnegative E. coli (MCRNEC), were characterized by phenotype and Illumina sequencing. A subset of MCRPEC was selected for MinION sequencing, conjugation assay, plasmid stability, and growth kinetics in vitro. The prevalence of MCRPEC was found to be 14.6% (98/673), with the highest prevalence in human rectal swabs (45.9% (45/98), p < 0.0001, odds ratio (OR): 0.125, 95% confidence interval (CI): 0.077–0.202). The percentages of MCRPEC from other samples were 14.3% (2/14) in dog feces, 12.0% (24/200) in flies, 11.0% (11/100) in chicken meat, 8.9% (8/90) in chicken cloacal, 8.0% (4/50) in chicken caeca, and 7.5% (4/53) in wastewater. MCRPEC was significantly more resistant to co-amoxiclav, sulfamethoxazoletrimethoprim, levofloxacin, ciprofloxacin, and gentamicin than MCRNEC (p < 0.05). Genomic analysis revealed the distribution of MCRPEC among diverse clonal types. The putative plasmid Inc types associated with mcr-1 were IncX4, IncHI2, IncP1, IncI2, and IncFIA, and those associated with mcr-3 were IncFII, IncFIA, IncFIB, IncP1, and IncR. Recovery of highly similar plasmids from both flies and other sampling sectors implied the role of flies in the dissemination of mcr-1. mcr-positive plasmids were shown to be conjugative, and a significantly high transfer rate into a hypervirulent clone ST1193 was observed. Plasmids containing mcr irrespective of Inc type were highly stable and invariably did not exert a fitness effect upon introduction into a new host. These findings signify the urgent need for a standard infection control program to radically decontaminate the source of resistance.
红霉素发酵菌渣长期施用对土壤耐药基因的累积影响 Article
韩子铭, 冯皓迪, 栾晓, 沈云鹏, 任立人, 邓留杰, D.G. Joakim Larsson, Michael Gillings, 张昱, 杨敏
《工程（英文）》 2022年 第15卷 第8期 页码 78-88 doi: 10.1016/j.eng.2022.05.011
王娜,郭欣妍,单正军,蔡道基
《中国工程科学》 2021年 第23卷 第1期 页码 167-173 doi: 10.15302/J-SSCAE-2021.01.023
抗生素在畜禽养殖业中发挥了重要保障作用，但畜禽粪便农用后伴生的抗生素耐药性传播风险日益显现，农田土壤抗生素及其耐药基因的风险管控工作亟待开展本文总结了农田土壤中抗生素的污染现状，梳理了农田土壤中新兴污染物抗生素管控存在的问题，提出了农田土壤抗生素及其耐药基因的风险管控建议。研究发现，农田土壤抗生素及其耐药基因的污染风险不可忽视，但抗生素类新兴污染物尚未纳入土壤风险管控范围内。应设立严格的兽药应用监管机制，从养殖源头扼制风险的发生概率；制定有机肥中反映耐药性的控制标准，出台技术指南以规范含抗生素粪便的处置与施用，减少抗生素耐药基因进入环境的总量。同时加紧开展环境抗生素耐药性产生和转移的人类健康风险评估研究，实施农田土壤环境抗生素耐药常规监测，发挥风险评估在该类污染物风险管控工作中的作用。
ARGs-OAP v3.0——抗生素耐药基因数据库的筛选和分析流程优化 Article
Xiaole Yin, Xiawan Zheng, Liguan Li, An-Ni Zhang, Xiao-Tao Jiang, Tong Zhang
《工程（英文）》 2023年 第27卷 第8期 页码 234-241 doi: 10.1016/j.eng.2022.10.011
Antibiotic resistance, which is encoded by antibiotic-resistance genes (ARGs), has proliferated to become a growing threat to public health around the world. With technical advances, especially in the popularization of metagenomic sequencing, scientists have gained the ability to decipher the profiles of ARGs in diverse samples with high accuracy at an accelerated speed. To analyze thousands of ARGs in a highthroughput way, standardized and integrated pipelines are needed. The new version (v3.0) of the widely used ARGs online analysis pipeline (ARGs-OAP) has made significant improvements to both the reference database—the structured ARGs (SARG) database—and the integrated analysis pipeline. SARG has been enhanced with sequence curation to improve annotation reliability, incorporate emerging resistance genotypes, and determine rigorous mechanism classification. The database has been further organized and visualized online in the format of a tree-like structure with a dictionary. It has also been divided into sub-databases for different application scenarios. In addition, the ARGs-OAP has been improved with adjusted quantification methods, simplified tool implementation, and multiple functions with userdefined reference databases. Moreover, the online platform now provides a diverse biostatistical analysis workflow with visualization packages for the efficient interpretation of ARG profiles. The ARGs-OAP v3.0 with an improved database and analysis pipeline will benefit academia, governmental management, and consultation regarding risk assessment of the environmental prevalence of ARGs.
关键词： SARG database ARGs-OAP Antibiotic-resistance genes Environmental metagenome Quantification
2014—2016年食品动物源RE-cmeABC阳性弯曲菌流行与耐药性现状 Article
刘德俊, 刘蔚雯, 李星, 姚红, 沈张奇, 汪洋, 沈建忠
《工程（英文）》 2020年 第6卷 第1期 页码 34-39 doi: 10.1016/j.eng.2019.10.013
关键词： RE- cmeABC 弯曲菌 环丙沙星 氟苯尼考
碳青霉烯类耐药性在人源和动物源产NDM酶大肠埃希菌间的传播 Article
沈应博, 胡付品, 王永强, 尹丹丹, 杨璐, 陈义强, 许春燕, 李基云, 蒋君瑶, 王雪杨, 付玉林, 邵东延, 刘德俊, 马藤菲, 蔡畅, 沈张奇, 王少林, 李娟, 张嵘, 柯跃斌, 吴聪明, 沈建忠, Timothy R. Walsh, 汪洋
《工程（英文）》 2022年 第15卷 第8期 页码 24-33 doi: 10.1016/j.eng.2021.07.030
Although carbapenem use is prohibited in animals in China, carbapenem-resistant Escherichia coli (CREC), especially New Delhi metallo-β-lactamase (NDM)-producing strains, are widely prevalent in foodproducing animals. At present, the impact of livestock-associated CREC strains on human populations at the national level is unknown. Here, we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence. We also ascertain the blaNDM and blaKPC abundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin. Overall, 631/29799 (2.1%) clinical Escherichia coli (E. coli) isolates were identified as CREC. Multivariable analysis revealed that being male, an age below 1, an age between 13 and 18, provinces with greater chicken production, and provinces with higher pig production were associated with higher odds of CREC infection. In general, 73.8% (n = 45/61) of pig farms and 62.2% (n = 28/45) of chicken farms had a blaNDM abundance of 1×10－5 to 1×10－3 and 1×10－3 to 1×10－2, respectively. Among all the Chinese NDM-positive E. coli (n = 463) available at the National Center for Biotechnology Information (NCBI), the genomic analysis revealed that blaNDM-5 and IncX3 were the predominant carbapenemase gene-plasmid combination, while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels. All the findings suggest frequent CREC transmission between humans and animals, indicating that further discussions on the use of antibiotics in animals and humans are needed, both in China and across the globe.
关键词： Carbapenem resistance Escherichia coli blaNDM-5 One Health Antimicrobial resistance transmission
应对可转移多黏菌素耐药性——饲料添加剂来源的白屈菜红碱具有双重效应 Article
宋黄威, 王雪杨, 张慕琛, 邹之宇, 杨思源, 易甜, 王建峰, 刘德俊, 沈应博, 代重山, 刘志海, Timothy R. Walsh, 沈建忠, 吴聪明, 汪洋
《工程（英文）》 2024年 第32卷 第1期 页码 163-173 doi: 10.1016/j.eng.2023.06.012
可转移多黏菌素耐药基因mcr-1及其变异体的出现、蔓延严重威胁了多黏菌素作为临床治疗多重耐药革兰阴性菌感染最后一道防线药物的药效寻找抗生素佐剂是恢复多黏菌素对其耐药菌敏感性的有效策略。然而，鲜有研究探索抗生素佐剂对多黏菌素耐药基因传播的影响。PMF），产生活性氧（reactive oxygen species, ROS），造成细菌胞内ATP耗竭，下调了mcr-1及接合转移相关基因的转录水平，从而实现既能增强多黏菌素对抗耐药菌作用，又能抑制耐药质粒接合转移的双重作用。白屈菜红碱的双重作用拓展了抗生素佐剂的应用范围，并提供了应对多黏菌素耐药的新思路。
标题 作者 时间 类型 操作
越南广平和顺化两省猪场分离副猪嗜血杆菌的抗生素耐药表型和耐药基因之间的相关性研究
Chao Nguyen Van, 张丽君, Tam Vu Thi Thanh, Hung Pham Hoang Son, Tuan Tran Ngoc, 黄琦, 周锐
期刊论文
猪链球菌中发现可介导链阳菌素A、截短侧耳素类以及林可酰胺类药物耐药的新型耐药基因 srpA
张朝阳, 刘璐, 张朋, 崔箐坡, 秦晓霞, 马立超, 韩坤, 王战辉, 王少林, 丁双阳, 沈张奇
期刊论文
基于同一健康策略探究老挝人、动物和环境中多黏菌素耐药性的传播特征
周宇晴, Refath Farzana, Somsavanh Sihalath, Sayaphet Rattanavong, Manivanh Vongsouvath, Mayfong Mayxay, Kirsty Sands, Paul N. Newton, David A.B. Dance, Brekhna Hassan, Timothy R. Walsh
期刊论文
红霉素发酵菌渣长期施用对土壤耐药基因的累积影响
韩子铭, 冯皓迪, 栾晓, 沈云鹏, 任立人, 邓留杰, D.G. Joakim Larsson, Michael Gillings, 张昱, 杨敏
期刊论文
ARGs-OAP v3.0——抗生素耐药基因数据库的筛选和分析流程优化
Xiaole Yin, Xiawan Zheng, Liguan Li, An-Ni Zhang, Xiao-Tao Jiang, Tong Zhang
期刊论文
2018—2019年我国北方地区奶牛临床型乳房炎源肺炎克雷伯菌的分子特征
宋士凯, 何文娟, 杨大伟, Manar Benmouffok, 王瑶, 李基云, 孙城涛, 宋祥彬, 马士珍, 蔡畅, 丁双阳, 吴聪明, 沈张奇, 汪洋
期刊论文
碳青霉烯类耐药性在人源和动物源产NDM酶大肠埃希菌间的传播
沈应博, 胡付品, 王永强, 尹丹丹, 杨璐, 陈义强, 许春燕, 李基云, 蒋君瑶, 王雪杨, 付玉林, 邵东延, 刘德俊, 马藤菲, 蔡畅, 沈张奇, 王少林, 李娟, 张嵘, 柯跃斌, 吴聪明, 沈建忠, Timothy R. Walsh, 汪洋
期刊论文
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