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革兰氏阴性菌生物膜：对抗生素负载混合聚合物胶束破坏的结构和功能反应

Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles.

作者信息

Damyanova Tsvetozara, Stancheva Rumena, Leseva Milena N, Dimitrova Petya A, Paunova-Krasteva Tsvetelina, Borisova Dayana, Kamenova Katya, Petrov Petar D, Veleva Ralitsa, Zhivkova Ivelina, Topouzova-Hristova Tanya, Haladjova Emi, Stoitsova Stoyanka

机构信息

Department of Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, Bulgaria.

Institute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 103-A, 1113 Sofia, Bulgaria.

出版信息

Microorganisms. 2024 Dec 23;12(12):2670. doi: 10.3390/microorganisms12122670.

DOI:10.3390/microorganisms12122670
PMID:39770872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11728461/
Abstract

Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA-b-PCL-b-PDMAEMA) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of and (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production).

摘要

生物膜是一种众所周知的多因素毒力因子，在慢性细菌感染中起关键作用。它们的致病性由菌株特异性毒力机制与生物膜细胞外基质（ECM）共同决定，这种基质可保护细菌免受宿主免疫防御及抗菌药物作用的影响。成功的抗生物膜药物应兼具抗菌活性和良好的生物相容性，并具备穿透ECM的能力。本研究的目的是构建破坏生物膜 - ECM的药物递送系统：基于阳离子聚（甲基丙烯酸2 - （二甲氨基）乙酯） - b - 聚（ε - 己内酯） - b - 聚（甲基丙烯酸2 - （二甲氨基）乙酯）（PDMAEMA - b - PCL - b - PDMAEMA）和非离子聚（环氧乙烷） - b - 聚（环氧丙烷） - b - 聚（环氧乙烷）（PEO - b - PPO - b - PEO）三嵌段共聚物的混合聚合物胶束（MPM），并负载环丙沙星或阿奇霉素。将MPM应用于金黄色葡萄球菌和铜绿假单胞菌（实验室菌株和临床分离株）预先形成24小时的生物膜上。结果表明，MPM能够破坏生物膜，活力实验支持了药物递送。生物膜对负载两种抗生素的MPM的反应揭示了两种不同的作用模式。这在细菌细胞结构改变（通过扫描电子显微镜证明）以及与宿主组织的相互作用（皮肤样本上的离体生物膜感染模型，检测一氧化氮和白细胞介素（IL） - 17A的产生）两个层面均有体现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/127cbd416c35/microorganisms-12-02670-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/22dcf61b6788/microorganisms-12-02670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/673898584a4d/microorganisms-12-02670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/458e1e3b0314/microorganisms-12-02670-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/394175a91a3d/microorganisms-12-02670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/e5dfac068512/microorganisms-12-02670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/af5fb10a7949/microorganisms-12-02670-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/20c2fa534aa4/microorganisms-12-02670-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/5521f9cdfbfb/microorganisms-12-02670-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/127cbd416c35/microorganisms-12-02670-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/22dcf61b6788/microorganisms-12-02670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/673898584a4d/microorganisms-12-02670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/458e1e3b0314/microorganisms-12-02670-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/394175a91a3d/microorganisms-12-02670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/e5dfac068512/microorganisms-12-02670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/af5fb10a7949/microorganisms-12-02670-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/20c2fa534aa4/microorganisms-12-02670-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/5521f9cdfbfb/microorganisms-12-02670-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15af/11728461/127cbd416c35/microorganisms-12-02670-g009.jpg

相似文献

[1]
Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles.

Microorganisms. 2024-12-23

[2]
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Pharmaceutics. 2023-4-4

[3]
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[4]
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ACS Nano. 2019-10-10

[5]
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Eng Life Sci. 2018-7-1

[6]
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Nanoscale. 2020-5-28

[7]
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[8]
Nanocarriers with conjugated antimicrobials to eradicate pathogenic biofilms evaluated in murine in vivo and human ex vivo infection models.

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[9]
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Mol Pharm. 2022-7-4

[10]
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Biomater Sci. 2018-11-20

本文引用的文献

[1]
Nanosized Complexes of the Proteolytic Enzyme Serratiopeptidase with Cationic Block Copolymer Micelles Enhance the Proliferation and Migration of Human Cells.

Pharmaceutics. 2024-7-25

[2]
A review of the mechanisms that confer antibiotic resistance in pathotypes of .

Front Cell Infect Microbiol. 2024

[3]
An Overview of Biofilm-Associated Infections and the Role of Phytochemicals and Nanomaterials in Their Control and Prevention.

Pharmaceutics. 2024-1-24

[4]
A surfactant-based dressing can reduce the appearance of Pseudomonas aeruginosa pigments and uncover the dermal extracellular matrix in an ex vivo porcine skin wound model.

Int Wound J. 2024-4

[5]
Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime-treated Pseudomonas aeruginosa acute pneumonia.

Microbiol Immunol. 2024-2

[6]
Microenvironment responsive charge-switchable nanoparticles act on biofilm eradication and virulence inhibition for chronic lung infection treatment.

J Control Release. 2024-1

[7]
Evaluation of antibiotic resistance, toxin-antitoxin systems, virulence factors, biofilm-forming strength and genetic linkage of Escherichia coli strains isolated from bloodstream infections of leukemia patients.

BMC Microbiol. 2023-11-4

[8]
Biofilm antimicrobial susceptibility testing: where are we and where could we be going?

Clin Microbiol Rev. 2023-12-20

[9]
Inhibition of IL-17 ameliorates keratinocyte-borne cytokine responses in an in vitro model for house-dust-mite triggered atopic dermatitis.

Sci Rep. 2023-10-3

[10]
Low-dose daylight exposure induces nitric oxide release and maintains cell viability in vitro.

Sci Rep. 2023-9-28

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