• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
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
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
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 @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

CRISPR 抑制脓肿分枝杆菌必需肽聚糖生物合成基因及其对β-内酰胺类药物敏感性的影响。

CRISPR Inhibition of Essential Peptidoglycan Biosynthesis Genes in Mycobacterium abscessus and Its Impact on β-Lactam Susceptibility.

机构信息

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.

Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.

出版信息

Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0009322. doi: 10.1128/aac.00093-22. Epub 2022 Mar 21.

DOI:10.1128/aac.00093-22
PMID:35311518
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9017322/
Abstract

We utilized a CRISPR interference (CRISPRi) assay to control the gene expressions of two predicted essential peptidoglycan biosynthesis genes, and , in Mycobacterium abscessus and to evaluate their contribution to β-lactam susceptibility. Our results showed that CRISPR inhibition of each gene led to a significant 3-log reduction in CFU in the presence of imipenem but not for cefoxitin. These results demonstrate that CRISPRi provides an experimental approach to study drug/target interactions in M. abscessus.

摘要

我们利用 CRISPR 干扰 (CRISPRi) 测定法来控制分枝杆菌中两种预测必需的肽聚糖生物合成基因和的基因表达,并评估它们对β-内酰胺类药物敏感性的贡献。我们的结果表明,CRISPR 对每个基因的抑制作用导致在亚胺培南存在时 CFU 显著减少 3 个对数,但对头孢西丁则没有。这些结果表明,CRISPRi 为研究分枝杆菌中的药物/靶标相互作用提供了一种实验方法。

相似文献

1
CRISPR Inhibition of Essential Peptidoglycan Biosynthesis Genes in Mycobacterium abscessus and Its Impact on β-Lactam Susceptibility.CRISPR 抑制脓肿分枝杆菌必需肽聚糖生物合成基因及其对β-内酰胺类药物敏感性的影响。
Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0009322. doi: 10.1128/aac.00093-22. Epub 2022 Mar 21.
2
Effect of β-lactamase production and β-lactam instability on MIC testing results for Mycobacterium abscessus.β-内酰胺酶的产生和β-内酰胺不稳定性对脓肿分枝杆菌 MIC 检测结果的影响。
J Antimicrob Chemother. 2017 Nov 1;72(11):3070-3078. doi: 10.1093/jac/dkx284.
3
Synergistic Interactions of Indole-2-Carboxamides and β-Lactam Antibiotics against Mycobacterium abscessus.吲哚-2-羧酰胺类化合物与β-内酰胺类抗生素对脓肿分枝杆菌的协同作用。
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02548-19.
4
"One-Two Punch": Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes."双拳出击":协同作用的β-内酰胺组合用于治疗脓肿分枝杆菌和抑制肽聚糖合成酶中的靶点冗余。
Clin Infect Dis. 2021 Oct 20;73(8):1532-1536. doi: 10.1093/cid/ciab535.
5
activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against .头孢西丁、亚胺培南、美罗培南和头孢洛林与沃博巴坦联合对. 的活性
Antimicrob Agents Chemother. 2024 May 2;68(5):e0017424. doi: 10.1128/aac.00174-24. Epub 2024 Apr 1.
6
Dual β-Lactam Combinations Highly Active against Mycobacterium abscessus Complex .双联β-内酰胺组合对脓肿分枝杆菌复合体高度有效。
mBio. 2019 Feb 12;10(1):e02895-18. doi: 10.1128/mBio.02895-18.
7
Select β-Lactam Combinations Exhibit Synergy against .选择β-内酰胺类抗生素联合用药具有协同作用。
Antimicrob Agents Chemother. 2019 Mar 27;63(4). doi: 10.1128/AAC.02613-18. Print 2019 Apr.
8
CRISPRi-mediated characterization of novel anti-tuberculosis targets: Mycobacterial peptidoglycan modifications promote beta-lactam resistance and intracellular survival.CRISPRi 介导的新型抗结核靶点表征:分枝杆菌肽聚糖修饰促进β-内酰胺类抗生素耐药性和细胞内存活。
Front Cell Infect Microbiol. 2023 Mar 15;13:1089911. doi: 10.3389/fcimb.2023.1089911. eCollection 2023.
9
Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates.新型β-内酰胺酶抑制剂雷利巴坦和沃巴坦与β-内酰胺类药物联合对脓肿分枝杆菌复合体临床分离株的活性。
Antimicrob Agents Chemother. 2019 Feb 26;63(3). doi: 10.1128/AAC.02623-18. Print 2019 Mar.
10
CRISPR Interference-Based Inhibition of MAB_0055c Expression Alters Drug Sensitivity in Mycobacterium abscessus.基于 CRISPR 干扰的 MAB_0055c 表达抑制改变了脓肿分枝杆菌中的药物敏感性。
Microbiol Spectr. 2023 Jun 15;11(3):e0063123. doi: 10.1128/spectrum.00631-23. Epub 2023 May 9.

引用本文的文献

1
Novel C5α-substituted carbapenems enhance killing via selective target binding and reduced hydrolysis by Bla.新型C5α取代碳青霉烯类药物通过选择性靶点结合和降低Bla水解作用增强杀菌效果。
Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0017025. doi: 10.1128/aac.00170-25. Epub 2025 Jun 17.
2
Harnessing CRISPR interference to resensitize laboratory strains and clinical isolates to last resort antibiotics.利用CRISPR干扰使实验室菌株和临床分离株对最后手段抗生素重新敏感。
Sci Rep. 2025 Jan 2;15(1):261. doi: 10.1038/s41598-024-81989-5.
3
Durlobactam in combination with β-lactams to combat .杜洛巴坦与β-内酰胺类联合使用以对抗……
Antimicrob Agents Chemother. 2025 Feb 13;69(2):e0117424. doi: 10.1128/aac.01174-24. Epub 2024 Dec 23.
4
CRISPR-Cas Systems in the Fight Against Antimicrobial Resistance: Current Status, Potentials, and Future Directions.对抗抗菌药物耐药性中的CRISPR-Cas系统:现状、潜力及未来方向
Infect Drug Resist. 2024 Nov 26;17:5229-5245. doi: 10.2147/IDR.S494327. eCollection 2024.
5
The CRISPR-dCas9 interference system suppresses inhA gene expression in Mycobacterium smegmatis.CRISPR-dCas9 干扰系统抑制耻垢分枝杆菌 inhA 基因的表达。
Sci Rep. 2024 Oct 30;14(1):26116. doi: 10.1038/s41598-024-77442-2.
6
Rapid Gene Silencing Followed by Antimicrobial Susceptibility Testing for Target Validation in Antibiotic Discovery.快速基因沉默及随后的抗菌药敏试验在抗生素发现中的靶标确证。
Methods Mol Biol. 2024;2833:23-33. doi: 10.1007/978-1-0716-3981-8_3.
7
CRISPR Interference-Mediated Silencing of the Gene in and Its Impact on Antimicrobial Susceptibility.CRISPR干扰介导的该基因在[具体对象]中的沉默及其对抗菌药物敏感性的影响。
Antibiotics (Basel). 2024 May 24;13(6):483. doi: 10.3390/antibiotics13060483.
8
Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against .舒巴坦与头孢呋辛或多尼培南联用对. 的协同作用
mBio. 2024 Jun 12;15(6):e0060924. doi: 10.1128/mbio.00609-24. Epub 2024 May 14.
9
activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against .头孢西丁、亚胺培南、美罗培南和头孢洛林与沃博巴坦联合对. 的活性
Antimicrob Agents Chemother. 2024 May 2;68(5):e0017424. doi: 10.1128/aac.00174-24. Epub 2024 Apr 1.
10
CRISPR-Cas-Based Antimicrobials: Design, Challenges, and Bacterial Mechanisms of Resistance.基于 CRISPR-Cas 的抗菌剂:设计、挑战和细菌耐药机制。
ACS Infect Dis. 2023 Jul 14;9(7):1283-1302. doi: 10.1021/acsinfecdis.2c00649. Epub 2023 Jun 22.

本文引用的文献

1
Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis.全基因组基因表达调控揭示了结核分枝杆菌的多种脆弱性。
Cell. 2021 Aug 19;184(17):4579-4592.e24. doi: 10.1016/j.cell.2021.06.033. Epub 2021 Jul 22.
2
Genome-Wide Essentiality Analysis of by Saturated Transposon Mutagenesis and Deep Sequencing.通过饱和转座子诱变和深度测序进行全基因组必需性分析。
mBio. 2021 Jun 29;12(3):e0104921. doi: 10.1128/mBio.01049-21. Epub 2021 Jun 15.
3
"One-Two Punch": Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes."双拳出击":协同作用的β-内酰胺组合用于治疗脓肿分枝杆菌和抑制肽聚糖合成酶中的靶点冗余。
Clin Infect Dis. 2021 Oct 20;73(8):1532-1536. doi: 10.1093/cid/ciab535.
4
Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus.非结核分枝杆菌与脓肿分枝杆菌的崛起。
Nat Rev Microbiol. 2020 Jul;18(7):392-407. doi: 10.1038/s41579-020-0331-1. Epub 2020 Feb 21.
5
Structures of Penicillin-Binding Protein 3 in Complex with Five -Lactam Antibiotics Reveal Mechanism of Inactivation.青霉素结合蛋白 3 与五种β-内酰胺抗生素复合物的结构揭示了失活机制。
Mol Pharmacol. 2020 Apr;97(4):287-294. doi: 10.1124/mol.119.118042. Epub 2020 Feb 21.
6
Non-tuberculous mycobacterial pulmonary disease.非结核分枝杆菌肺病。
Eur Respir J. 2019 Jul 11;54(1). doi: 10.1183/13993003.00250-2019. Print 2019 Jul.
7
Synergistic Efficacy of β-Lactam Combinations against Pulmonary Infection in Mice.β-内酰胺类抗生素联合用药对小鼠肺部感染的协同疗效。
Antimicrob Agents Chemother. 2019 Jul 25;63(8). doi: 10.1128/AAC.00614-19. Print 2019 Aug.
8
Dual β-Lactam Combinations Highly Active against Mycobacterium abscessus Complex .双联β-内酰胺组合对脓肿分枝杆菌复合体高度有效。
mBio. 2019 Feb 12;10(1):e02895-18. doi: 10.1128/mBio.02895-18.
9
Select β-Lactam Combinations Exhibit Synergy against .选择β-内酰胺类抗生素联合用药具有协同作用。
Antimicrob Agents Chemother. 2019 Mar 27;63(4). doi: 10.1128/AAC.02613-18. Print 2019 Apr.
10
and β-Lactams: Emerging Insights and Potential Opportunities.以及β-内酰胺类:新见解与潜在机遇
Front Microbiol. 2018 Sep 25;9:2273. doi: 10.3389/fmicb.2018.02273. eCollection 2018.