旧药新用：在抗生素后时代产生针对多重耐药革兰氏阴性菌的抗体
A New Take on an Old Remedy: Generating Antibodies against Multidrug-Resistant Gram-Negative Bacteria in a Postantibiotic World.
作者信息
Motley Michael P, Fries Bettina C
机构信息
Division of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.
出版信息
mSphere. 2017 Oct 4;2(5). doi: 10.1128/mSphere.00397-17. eCollection 2017 Sep-Oct.
Abstract
With the problem of multidrug-resistant Gram-negative pathogens becoming increasingly dire, new strategies are needed to protect and treat infected patients. Though abandoned in the past, monoclonal antibody therapy against Gram-negative bacteria remains a potential solution and has potential advantages over the broad-spectrum antibiotics they were once replaced by. This Perspective reviews the prospect of utilizing monoclonal antibody therapy against these pathogens, as well as the challenges of doing so and the current therapy targets under investigation.
摘要
随着多重耐药革兰氏阴性病原体问题日益严峻，需要新的策略来保护和治疗受感染患者。尽管单克隆抗体疗法过去曾被放弃，但针对革兰氏阴性菌的单克隆抗体疗法仍是一种潜在的解决方案，并且相对于它们曾经所取代的广谱抗生素具有潜在优势。本观点文章综述了利用单克隆抗体疗法对抗这些病原体的前景，以及这样做所面临的挑战和目前正在研究的治疗靶点。
相似文献
1
A New Take on an Old Remedy: Generating Antibodies against Multidrug-Resistant Gram-Negative Bacteria in a Postantibiotic World.旧药新用：在抗生素后时代产生针对多重耐药革兰氏阴性菌的抗体
mSphere. 2017 Oct 4;2(5). doi: 10.1128/mSphere.00397-17. eCollection 2017 Sep-Oct.
2
Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant Klebsiella pneumoniae Protect from Infection.新型广谱抗碳青霉烯类耐药肺炎克雷伯菌荚膜抗体可预防感染。
mBio. 2018 Apr 3;9(2):e00091-18. doi: 10.1128/mBio.00091-18.
3
Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial.作为替加环素评估与监测试验的一部分，2004年至2014年期间替加环素对多重耐药革兰氏阴性病原菌活性的全球评估
mSphere. 2017 Jan 18;2(1). doi: 10.1128/mSphere.00310-16. eCollection 2017 Jan-Feb.
4
Sulopenem: An Intravenous and Oral Penem for the Treatment of Urinary Tract Infections Due to Multidrug-Resistant Bacteria.舒巴坦钠：一种用于治疗多重耐药菌引起的尿路感染的静脉注射和口服青霉素类药物。
Drugs. 2022 Apr;82(5):533-557. doi: 10.1007/s40265-022-01688-1. Epub 2022 Mar 16.
5
Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review.新冠疫情对耐多药革兰阳性和革兰阴性病原体的影响：系统综述。
J Infect Public Health. 2023 Mar;16(3):320-331. doi: 10.1016/j.jiph.2022.12.022. Epub 2022 Dec 31.
6
The Role of IgG Subclass in Antibody-Mediated Protection against Carbapenem-Resistant Klebsiella pneumoniae.IgG 亚类在抗碳青霉烯类耐药肺炎克雷伯菌抗体介导的保护中的作用。
mBio. 2020 Sep 8;11(5):e02059-20. doi: 10.1128/mBio.02059-20.
7
Multidrug resistance in Gram-negative pathogens isolated from patients with chronic kidney diseases and renal transplant.
J Pak Med Assoc. 2018 Apr;68(4):642-645.
8
High Level of Multidrug-Resistant Gram-Negative Pathogens Causing Burn Wound Infections in Hospitalized Children in Dar es Salaam, Tanzania.坦桑尼亚达累斯萨拉姆住院儿童烧伤创面感染中多重耐药革兰氏阴性病原菌的高流行率
Int J Microbiol. 2021 Jul 2;2021:6644185. doi: 10.1155/2021/6644185. eCollection 2021.
9
[Microbiological profiles of pathogens causing nosocomial bacteremia in 2011, 2013 and 2016].[2011年、2013年和2016年医院获得性菌血症病原菌的微生物学特征]
Sheng Wu Gong Cheng Xue Bao. 2018 Aug 25;34(8):1205-1217. doi: 10.13345/j.cjb.180192.
10
Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding.通过破坏细胞外蛋白质折叠来打破抗微生物药物耐药性。
Elife. 2022 Jan 13;11:e57974. doi: 10.7554/eLife.57974.
引用本文的文献
1
Urinary Multidrug-Resistant : Essential Oil Countermeasures in a One Health Case Report.泌尿道多重耐药：“同一健康”案例报告中的精油应对措施
Microorganisms. 2025 Aug 1;13(8):1807. doi: 10.3390/microorganisms13081807.
2
Mechanisms, therapeutic strategies, and emerging therapeutic alternatives for carbapenem resistance in Gram-negative bacteria.革兰氏阴性菌对碳青霉烯类耐药的机制、治疗策略及新兴治疗选择
Arch Microbiol. 2025 Feb 13;207(3):58. doi: 10.1007/s00203-025-04252-z.
3
Monoclonal antibodies: From magic bullet to precision weapon.单克隆抗体：从“魔弹”到“精准武器”。
Mol Biomed. 2024 Oct 11;5(1):47. doi: 10.1186/s43556-024-00210-1.
4
Anti-Acinetobacter Baumannii single-chain variable fragments provide therapeutic efficacy in an immunocompromised mouse pneumonia model.抗鲍曼不动杆菌单链可变片段在免疫抑制小鼠肺炎模型中具有治疗效果。
BMC Microbiol. 2024 Feb 10;24(1):55. doi: 10.1186/s12866-023-03080-9.
5
Development of an anti- therapeutic monoclonal antibody WVDC-5244.抗治疗性单克隆抗体 WVDC-5244 的研发。
Front Cell Infect Microbiol. 2023 Apr 14;13:1117844. doi: 10.3389/fcimb.2023.1117844. eCollection 2023.
6
Role of alternatives to antibiotics in mitigating the antimicrobial resistance crisis.抗生素替代品在缓解抗菌药物耐药性危机中的作用。
Indian J Med Res. 2022 Sep;156(3):464-477. doi: 10.4103/ijmr.IJMR_3514_20.
7
The Exploration of Complement-Resistance Mechanisms of Pathogenic Gram-Negative Bacteria to Support the Development of Novel Therapeutics.致病性革兰氏阴性菌补体抗性机制的探索以支持新型疗法的开发
Pathogens. 2022 Aug 18;11(8):931. doi: 10.3390/pathogens11080931.
8
Patient-Derived Antibody Data Yields Development of Broadly Cross-Protective Monoclonal Antibody against ST258 Carbapenem-Resistant .患者来源抗体数据可开发针对 ST258 碳青霉烯类耐药菌的广泛交叉保护单克隆抗体
Microbiol Spectr. 2022 Aug 31;10(4):e0176022. doi: 10.1128/spectrum.01760-22. Epub 2022 Jul 11.
9
Structure-activity relationship studies of [1,2,5]oxadiazolo[3,4-b]pyrazine-containing polymyxin-selective resistance-modifying agents.含[1,2,5]噁二唑并[3,4-b]吡嗪的多黏菌素选择性耐药修饰剂的构效关系研究。
Bioorg Med Chem Lett. 2022 Sep 15;72:128878. doi: 10.1016/j.bmcl.2022.128878. Epub 2022 Jul 3.
10
Monoclonal antibody therapeutics for infectious diseases: Beyond normal human immunoglobulin.单克隆抗体治疗传染病：超越正常人类免疫球蛋白。
Pharmacol Ther. 2022 Dec;240:108233. doi: 10.1016/j.pharmthera.2022.108233. Epub 2022 Jun 20.
本文引用的文献
1
Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4.抗脂多糖抗体通过增强中性粒细胞介导的清除作用而不中和Toll样受体4来抵御肺炎克雷伯菌。
JCI Insight. 2017 May 4;2(9). doi: 10.1172/jci.insight.92774.
2
The diversity of surface polysaccharides.表面多糖的多样性。
Microb Genom. 2016 Aug 25;2(8):e000073. doi: 10.1099/mgen.0.000073. eCollection 2016 Aug.
3
Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States.美国碳青霉烯类耐药肠杆菌科细菌（CRE）感染中心地区耐碳青霉烯类肠杆菌科细菌（CRE）所致菌血症的多中心临床与分子流行病学分析
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02349-16. Print 2017 Apr.
4
Anti-MrkA Monoclonal Antibodies Reveal Distinct Structural and Antigenic Features of MrkA.抗MrkA单克隆抗体揭示了MrkA独特的结构和抗原特征。
PLoS One. 2017 Jan 20;12(1):e0170529. doi: 10.1371/journal.pone.0170529. eCollection 2017.
5
Endotoxin neutralization by an O-antigen specific monoclonal antibody: A potential novel therapeutic approach against Klebsiella pneumoniae ST258.O抗原特异性单克隆抗体对内毒素的中和作用：一种针对肺炎克雷伯菌ST258的潜在新型治疗方法。
Virulence. 2017 Oct 3;8(7):1203-1215. doi: 10.1080/21505594.2017.1279778. Epub 2017 Jan 19.
6
Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae.基于抗体的免疫疗法治疗和预防高毒力肺炎克雷伯菌感染
Clin Vaccine Immunol. 2017 Jan 5;24(1). doi: 10.1128/CVI.00456-16. Print 2017 Jan.
7
Therapeutic monoclonal antibodies and derivatives: Historical perspectives and future directions.治疗性单克隆抗体及其衍生物：历史回顾与未来展望。
Biotechnol Adv. 2016 Nov 1;34(6):1149-1158. doi: 10.1016/j.biotechadv.2016.07.004. Epub 2016 Jul 25.
8
Ig Constant Region Effects on Variable Region Structure and Function.免疫球蛋白恒定区对可变区结构和功能的影响。
Front Microbiol. 2016 Feb 4;7:22. doi: 10.3389/fmicb.2016.00022. eCollection 2016.
9
Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii.用一种22千道尔顿的外膜蛋白进行免疫接种可引发对多重耐药鲍曼不动杆菌的保护性免疫。
Sci Rep. 2016 Feb 8;6:20724. doi: 10.1038/srep20724.
10
Target-Agnostic Identification of Functional Monoclonal Antibodies Against Klebsiella pneumoniae Multimeric MrkA Fimbrial Subunit.针对肺炎克雷伯菌多聚体MrkA菌毛亚基的功能性单克隆抗体的无靶点鉴定
J Infect Dis. 2016 Jun 1;213(11):1800-8. doi: 10.1093/infdis/jiw021. Epub 2016 Jan 14.
Zotero 插件