دورية أكاديمية
Development of a transcription factor decoy-nanocarrier system as a successful inhibitor of Enterococcus faecalis virulence in vitro and in vivo.
| العنوان: | Development of a transcription factor decoy-nanocarrier system as a successful inhibitor of Enterococcus faecalis virulence in vitro and in vivo. |
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| المؤلفون: | Badr EA; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Nagy YI; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Sayed RM; Natural Products Research Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt., Kashef MT; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. Electronic address: mona.kashef@pharma.cu.edu.eg. |
| المصدر: | Microbial pathogenesis [Microb Pathog] 2024 Aug; Vol. 193, pp. 106762. Date of Electronic Publication: 2024 Jun 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: England NLM ID: 8606191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1208 (Electronic) Linking ISSN: 08824010 NLM ISO Abbreviation: Microb Pathog Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London ; Orlando : Academic Press, c1986- |
| مواضيع طبية MeSH: | Enterococcus faecalis*/drug effects , Enterococcus faecalis*/genetics , Quorum Sensing*/drug effects , Gram-Positive Bacterial Infections*/microbiology , Gram-Positive Bacterial Infections*/drug therapy , Bacterial Proteins*/genetics , Bacterial Proteins*/metabolism, Animals ; Virulence/drug effects ; Humans ; Anti-Bacterial Agents/pharmacology ; Liposomes ; Larva/microbiology ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Virulence Factors/genetics ; Gelatinases/metabolism ; Gelatinases/antagonists & inhibitors ; Moths/microbiology ; Erythrocytes/drug effects ; Disease Models, Animal ; Serine Proteases/metabolism ; Serine Proteases/genetics ; Gene Expression Regulation, Bacterial/drug effects ; Nanoparticles/chemistry ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism |
| مستخلص: | Enterococcus faecalis is a troublesome nosocomial pathogen that acquired resistance to most available antimicrobial agents. Antivirulence agents represent an unconventional treatment approach. Here, transcription factor decoy (TFD)-loaded cationic liposomes (TLL) were developed as an inhibitor of the Fsr quorum-sensing system and its associated virulence traits, in E. faecalis. The consensus sequence of the FsrA binding site was found conserved among 651 E. faecalis annotated genomes. The TFD was synthesized as an 82 bp DNA duplex, containing the conserved binding sequence, and loaded onto cationic liposomes. The optimum loading capacity, mean particle size, and zeta potential of the TLL were characterized. The developed TLL lacked any effect on E. faecalis growth and significantly inhibited the in vitro production of the proteolytic enzymes controlled by the Fsr system; gelatinase and serine protease, in a concentration-dependent manner. This inhibition was accompanied by a significant reduction in the transcription levels of FsrA-regulated genes (fsrB, gelE, and sprE). The developed TLL were safe as evidenced by the nonhemolytic effect on human RBCs and the negligible cytotoxicity on human skin fibroblast cells. Moreover, in the larvae infection model, TLL displayed a significant abolish in the mortality rates of Galleria mellonella larvae infected with E. faecalis. In conclusion, the developed TLL offer a new safe strategy for combating E. faecalis infection through the inhibition of quorum-sensing-mediated virulence; providing a platform for the development of similar agents to combat many other pathogens. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antivirulence; Cationic liposomes; Enterococcus faecalis; Gelatinase; Serine protease; Transcription factor decoy |
| المشرفين على المادة: | 0 (Bacterial Proteins) 0 (Anti-Bacterial Agents) 0 (Liposomes) 0 (Transcription Factors) 0 (Virulence Factors) EC 3.4.24.- (Gelatinases) 0 (FsrB protein, Enterococcus) EC 3.4.- (Serine Proteases) EC 3.4.21.- (Serine Endopeptidases) |
| تواريخ الأحداث: | Date Created: 20240627 Date Completed: 20240722 Latest Revision: 20240722 |
| رمز التحديث: | 20240723 |
| DOI: | 10.1016/j.micpath.2024.106762 |
| PMID: | 38936638 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-1208 |
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| DOI: | 10.1016/j.micpath.2024.106762 |