• 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

过表达 OmpR 和下调 OmpK35 导致替加环素耐药肺炎克雷伯菌毒力降低。

Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35.

机构信息

Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.

Department of Advanced Bioconvergence Product, Ministry of Food and Drug Safety, Cheongju, 28159, Republic of Korea.

出版信息

J Biomed Sci. 2023 Mar 31;30(1):22. doi: 10.1186/s12929-023-00910-w.

DOI:10.1186/s12929-023-00910-w
PMID:37004036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10064660/
Abstract

BACKGROUND

The development of tigecycline resistance in hypervirulent Klebsiella pneumoniae strains has resulted in decreased virulence that is associated with reduced production of capsular polysaccharides (CPS). In this study, we investigated the mechanisms that link tigecycline susceptibility to decreased virulence.

METHODS

We compared transcriptomes from tigecycline-susceptible wild-type strains and tigecycline-resistant mutants using mRNA sequencing. ompR-overexpressed and ompR-deleted mutants were constructed from wild-type strains and tigecycline-resistant mutants, respectively. Antibiotic susceptibility tests were performed, and string tests and precipitation assays were conducted to identify phenotypic changes related to tigecycline susceptibility and ompR expression. Bacterial virulence was assessed by serum resistance and Galleria mellonella infection assays.

RESULTS

Transcriptomic analyses demonstrated a significant decrease in the expression of ompK35 in the tigecycline-resistant mutants. We observed that tigecycline-resistant mutants overexpressed ompR, and that the expression of ompK35 was regulated negatively by ompR. While tigecycline-resistant mutants and ompR-overexpressed mutants exhibited reduced hypermucoviscosity and virulence, deletion of ompR from tigecycline-resistant mutants restored their hypermucoviscosity and virulence.

CONCLUSIONS

In hypervirulent K. pneumoniae strains, ompR expression, which is regulated by exposure to tigecycline, may affect the production of CPS, leading to bacterial virulence.

摘要

背景

高产毒肺炎克雷伯菌菌株中替加环素耐药性的发展导致毒力降低，这与荚膜多糖（CPS）产量减少有关。在这项研究中，我们研究了将替加环素敏感性与降低的毒力联系起来的机制。

方法

我们使用 mRNA 测序比较了替加环素敏感野生型菌株和替加环素耐药突变体的转录组。分别从野生型菌株和替加环素耐药突变体中构建了 ompR 过表达和 ompR 缺失突变体。进行抗生素敏感性试验，进行字符串试验和沉淀试验，以鉴定与替加环素敏感性和 ompR 表达相关的表型变化。通过血清抗性和大蜡螟感染试验评估细菌毒力。

结果

转录组分析表明替加环素耐药突变体中 ompK35 的表达显著降低。我们观察到替加环素耐药突变体过表达 ompR，并且 ompK35 的表达受 ompR 负调控。虽然替加环素耐药突变体和 ompR 过表达突变体表现出低黏液高粘性和低毒力，但从替加环素耐药突变体中缺失 ompR 恢复了它们的黏液高粘性和毒力。

结论

在高产毒肺炎克雷伯菌菌株中，ompR 的表达可能受替加环素暴露的调节，可能会影响 CPS 的产生，从而导致细菌毒力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/001bad66b3a0/12929_2023_910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/33b8363597e4/12929_2023_910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/9d6cb502c5b6/12929_2023_910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/75db9cdf2735/12929_2023_910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/26377f65fd5b/12929_2023_910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/001bad66b3a0/12929_2023_910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/33b8363597e4/12929_2023_910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/9d6cb502c5b6/12929_2023_910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/75db9cdf2735/12929_2023_910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/26377f65fd5b/12929_2023_910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8299/10064660/001bad66b3a0/12929_2023_910_Fig5_HTML.jpg

相似文献

1
Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35.过表达 OmpR 和下调 OmpK35 导致替加环素耐药肺炎克雷伯菌毒力降低。
J Biomed Sci. 2023 Mar 31;30(1):22. doi: 10.1186/s12929-023-00910-w.
2
Emergence of Tigecycline Nonsusceptible and IMP-4 Carbapenemase-Producing K2-ST65 Hypervirulent Klebsiella pneumoniae in China.中国出现对替加环素不敏感和产IMP-4 碳青霉烯酶的 K2-ST65 高毒力肺炎克雷伯菌。
Microbiol Spectr. 2021 Oct 31;9(2):e0130521. doi: 10.1128/Spectrum.01305-21. Epub 2021 Oct 27.
3
Conversion to colistin susceptibility by tigecycline exposure in colistin-resistant Klebsiella pneumoniae and its implications to combination therapy.替加环素暴露使多黏菌素耐药肺炎克雷伯菌转为对多黏菌素敏感及其对联合治疗的意义。
Int J Antimicrob Agents. 2024 Jan;63(1):107017. doi: 10.1016/j.ijantimicag.2023.107017. Epub 2023 Oct 25.
4
Change of Hypermucoviscosity in the Development of Tigecycline Resistance in Hypervirulent Sequence Type 23 Strains.高毒力序列型23菌株中替加环素耐药性发展过程中超粘液性的变化
Microorganisms. 2020 Oct 10;8(10):1562. doi: 10.3390/microorganisms8101562.
5
Two-Component Response Regulator OmpR Regulates Mucoviscosity through Energy Metabolism in Klebsiella pneumoniae.双组分调控子 OmpR 通过能量代谢调节肺炎克雷伯菌的黏液性。
Microbiol Spectr. 2023 Jun 15;11(3):e0054423. doi: 10.1128/spectrum.00544-23. Epub 2023 Apr 25.
6
Tigecycline-non-susceptible hypervirulent Klebsiella pneumoniae strains in Taiwan.台湾地区对替加环素不敏感的高毒力肺炎克雷伯菌。
J Antimicrob Chemother. 2020 Feb 1;75(2):309-317. doi: 10.1093/jac/dkz450.
7
Coexistence of tet(A) and bla in the ST11 hypervirulent tigecycline- and carbapenem-resistant Klebsiella pneumoniae isolated from a blood sample.从血样中分离出一株对替加环素和碳青霉烯类药物高度耐药的超毒力肺炎克雷伯菌，该菌同时携带 tet(A)和 bla。
Eur J Clin Microbiol Infect Dis. 2023 Jan;42(1):23-31. doi: 10.1007/s10096-022-04512-6. Epub 2022 Nov 2.
8
In vivo evolution of tigecycline-non-susceptible Klebsiella pneumoniae strains in patients: relationship between virulence and resistance.患者体内对替加环素不敏感的肺炎克雷伯菌菌株的进化：毒力与耐药性之间的关系。
Int J Antimicrob Agents. 2016 Nov;48(5):485-491. doi: 10.1016/j.ijantimicag.2016.07.008. Epub 2016 Aug 15.
9
Unravelling the genome sequence of a pandrug-resistant Klebsiella pneumoniae isolate with sequence type 11 and capsular serotype KL64 from China.解析一株来自中国的携带 11 型序列和 KL64 荚膜血清型的泛耐药肺炎克雷伯菌的基因组序列。
J Glob Antimicrob Resist. 2019 Dec;19:40-42. doi: 10.1016/j.jgar.2019.08.013. Epub 2019 Aug 23.
10
ramR mutations in clinical isolates of Klebsiella pneumoniae with reduced susceptibility to tigecycline.肺炎克雷伯菌临床分离株中对替加环素耐药性降低与 ramR 突变有关。
Antimicrob Agents Chemother. 2010 Jun;54(6):2720-3. doi: 10.1128/AAC.00085-10. Epub 2010 Mar 29.

引用本文的文献

1
Molecular epidemiology and clinical characteristics of carbapenem-resistant bloodstream and pneumonia isolates.耐碳青霉烯类血流感染和肺炎分离株的分子流行病学及临床特征
Microbiol Spectr. 2025 Aug 5;13(8):e0063125. doi: 10.1128/spectrum.00631-25. Epub 2025 Jul 9.
2
Exploring current hypervirulent infections: insights into pathogenesis, drug resistance, and vaccine prospects.探索当前的高毒力感染：对发病机制、耐药性及疫苗前景的见解
Front Microbiol. 2025 May 29;16:1604763. doi: 10.3389/fmicb.2025.1604763. eCollection 2025.
3
Effect of colistin-tigecycline combination on colistin-resistant and carbapenem-resistant and .

本文引用的文献

1
High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae.高渗透压通过调节 KvBvR 增加 OmpK36 表达从而降低肺炎克雷伯菌的抗菌耐药性。
Microbiol Spectr. 2022 Jun 29;10(3):e0050722. doi: 10.1128/spectrum.00507-22. Epub 2022 Jun 6.
2
Genomic and Phenotypic Evolution of Tigecycline-Resistant Acinetobacter baumannii in Critically Ill Patients.重症患者中替加环素耐药鲍曼不动杆菌的基因组和表型演变。
Microbiol Spectr. 2022 Feb 23;10(1):e0159321. doi: 10.1128/spectrum.01593-21. Epub 2022 Jan 19.
3
Emergence of tigecycline-resistant Klebsiella pneumoniae ST11 clone in patients without exposure to tigecycline.
黏菌素-替加环素联合用药对耐黏菌素和耐碳青霉烯类的影响及……（原文最后不完整）
Microbiol Spectr. 2025 Feb 4;13(2):e0202124. doi: 10.1128/spectrum.02021-24. Epub 2024 Dec 19.
4
Third-Generation Tetracyclines: Current Knowledge and Therapeutic Potential.第三代四环素类药物：现有知识和治疗潜力。
Biomolecules. 2024 Jun 30;14(7):783. doi: 10.3390/biom14070783.
5
Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria.革兰氏阴性菌抗生素耐药机制的评估
Antibiotics (Basel). 2023 Nov 3;12(11):1590. doi: 10.3390/antibiotics12111590.
耐替加环素肺炎克雷伯菌 ST11 克隆在未接触替加环素的患者中的出现。
J Infect Dev Ctries. 2021 Nov 30;15(11):1677-1684. doi: 10.3855/jidc.15157.
4
An outbreak of ertapenem-resistant, carbapenemase-negative and porin-deficient ESBL-producing complex.耐厄他培南、碳青霉烯酶阴性且孔蛋白缺陷的产超广谱β-内酰胺酶菌的暴发。
Germs. 2021 Jun 2;11(2):199-210. doi: 10.18683/germs.2021.1257. eCollection 2021 Jun.
5
Klebsiella pneumoniae enolase-like membrane protein interacts with human plasminogen.肺炎克雷伯菌烯醇化酶样膜蛋白与人纤溶酶原相互作用。
Int J Med Microbiol. 2021 Aug;311(6):151518. doi: 10.1016/j.ijmm.2021.151518. Epub 2021 Jul 3.
6
Resistance evolution of hypervirulent carbapenem-resistant ST11 during treatment with tigecycline and polymyxin.碳青霉烯类药物耐药超毒力 ST11 在替加环素和黏菌素治疗过程中的耐药演变。
Emerg Microbes Infect. 2021 Dec;10(1):1129-1136. doi: 10.1080/22221751.2021.1937327.
7
Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review.替加环素的抗菌活性、临床疗效以及耐药机制和流行病学：叙述性综述。
Eur J Clin Microbiol Infect Dis. 2022 Jul;41(7):1003-1022. doi: 10.1007/s10096-020-04121-1. Epub 2021 Jan 5.
8
Change of Hypermucoviscosity in the Development of Tigecycline Resistance in Hypervirulent Sequence Type 23 Strains.高毒力序列型23菌株中替加环素耐药性发展过程中超粘液性的变化
Microorganisms. 2020 Oct 10;8(10):1562. doi: 10.3390/microorganisms8101562.
9
Population genomics of Klebsiella pneumoniae.肺炎克雷伯氏菌的群体基因组学。
Nat Rev Microbiol. 2020 Jun;18(6):344-359. doi: 10.1038/s41579-019-0315-1. Epub 2020 Feb 13.
10
A Klebsiella pneumoniae Regulatory Mutant Has Reduced Capsule Expression but Retains Hypermucoviscosity.肺炎克雷伯氏菌调节突变株表达荚膜减少但仍具有超黏液性。
mBio. 2019 Mar 26;10(2):e00089-19. doi: 10.1128/mBio.00089-19.