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用于筛选抗耐药菌单克隆抗体的高通量杀菌试验

High-throughput bactericidal assays for monoclonal antibody screening against antimicrobial resistant .

作者信息

Stazzoni Samuele, Troisi Marco, Abbiento Valentina, Sala Claudia, Andreano Emanuele, Rappuoli Rino

机构信息

Monoclonal Antibody Discovery Laboratory, Fondazione Toscana Life Sciences, Siena, Italy.

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.

出版信息

Front Microbiol. 2023 Aug 16;14:1243427. doi: 10.3389/fmicb.2023.1243427. eCollection 2023.

DOI:10.3389/fmicb.2023.1243427
PMID:37655342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10466782/
Abstract

(gonococcus) is an obligate human pathogen and the etiological agent of the sexually transmitted disease gonorrhea. The rapid rise in gonococcal resistance to all currently available antimicrobials has become a significant public health burden and the need to develop novel therapeutic and prophylactic tools is now a global priority. While high-throughput screening methods allowed rapid discovery of extremely potent monoclonal antibodies (mAbs) against viral pathogens, the field of bacteriology suffers from the lack of assays that allow efficient screening of large panels of samples. To address this point, we developed luminescence-based (L-ABA) and resazurin-based (R-ABA) antibody bactericidal assays that measure metabolic activity as a proxy of bacterial viability. Both L-ABA and R-ABA are applicable on the large scale for the rapid identification of bactericidal antibodies and were validated by conventional methods. Implementation of these approaches will be instrumental to the development of new medications and vaccines against and other bacterial pathogens to support the fight against antimicrobial resistance.

摘要

淋球菌是一种 obligate human pathogen,也是性传播疾病淋病的病原体。淋球菌对所有现有抗菌药物的耐药性迅速上升,已成为一项重大的公共卫生负担,开发新型治疗和预防工具的需求现已成为全球优先事项。虽然高通量筛选方法能够快速发现针对病毒病原体的极其有效的单克隆抗体(mAb),但细菌学领域缺乏能够高效筛选大量样本的检测方法。为了解决这一问题,我们开发了基于发光的(L-ABA)和基于刃天青的(R-ABA)抗体杀菌检测方法,这些方法通过测量代谢活性来替代细菌活力。L-ABA 和 R-ABA 均可大规模应用于快速鉴定杀菌抗体,并已通过传统方法进行验证。实施这些方法将有助于开发针对淋病及其他细菌病原体的新药物和疫苗,以支持对抗抗菌药物耐药性的斗争。

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Cell. 2021 Apr 1;184(7):1821-1835.e16. doi: 10.1016/j.cell.2021.02.035. Epub 2021 Feb 23.
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Intra-Laboratory Evaluation of Luminescence Based High-Throughput Serum Bactericidal Assay (L-SBA) to Determine Bactericidal Activity of Human Sera against .基于发光的高通量血清杀菌试验(L-SBA)在实验室内部的评估,以确定人血清对……的杀菌活性
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以大流行的速度开发治疗性单克隆抗体。
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Progress Toward a Gonococcal Vaccine: The Way Forward.迈向淋球菌疫苗的进展:前进之路。
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Epidemiology of gonorrhoea: a global perspective.淋病的流行病学:全球视角
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Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody.补体单独驱动嵌合抗淋球菌单克隆抗体的疗效。
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