Ming Wei, Peng Wang, Tianmeng Li, Jun Liu, Yu Wang, Li Gu, Shuai Wang
{"title":"转录组分析揭示了γ-亚麻酸根除万古霉素耐药粪肠球菌生物膜的分子机制。","authors":"Ming Wei, Peng Wang, Tianmeng Li, Jun Liu, Yu Wang, Li Gu, Shuai Wang","doi":"10.3389/fcimb.2025.1525581","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Vancomycin-resistant <i>Enterococcus faecium</i> (VRE-fm) biofilms pose a significant clinical challenge due to the limited effectiveness of traditional antibiotics. This study investigates the potential of γ-linolenic acid (GLA) as a novel antibiofilm agent.</p><p><strong>Methods: </strong>Transcriptome analysis was performed on the V27 isolate, comparing cells in mature biofilms treated with and without GLA. The findings were further validated using qRT-PCR on six VRE-fm isolates and two <i>E. faecalis</i> isolates.</p><p><strong>Results: </strong>Transcriptome analysis revealed a significant downregulation in the expression levels of genes associated with biofilm formation, including <i>fruA</i>, <i>fruB</i>, <i>sgrA</i>, <i>lpxtg-cwa</i>, <i>tfpp</i>, <i>lafA</i>, <i>lafB</i>, <i>malP</i>, <i>fsrA</i>, and <i>fsrC'</i>, while a significant upregulation was observed in the expression of <i>fsrBD</i>. Validation by qRT-PCR in six VRE-fm isolates confirmed the significant changes in the expression levels of all genes except for <i>lpxtg-cwa</i>, with statistical significance. The expression of <i>bgsB</i> and <i>bgsA</i> genes, which are the homologs of <i>lafA</i> and <i>lafB</i> genes, along with the Fsr-regulated genes <i>gelE</i> and <i>sprE</i> in <i>E. faecalis</i>, were also found to be downregulated by GLA. In addition, KEGG analysis identified specific metabolic pathways that were significantly downregulated by GLA.</p><p><strong>Conclusion: </strong>GLA effectively targets multiple aspects of biofilm formation in VRE-fm, including the downregulation of key biofilm-related genes, the inhibition of quorum sensing systems, and the modulation of metabolic pathways. GLA emerges as a promising candidate for eradicating <i>Enterococcus</i> biofilms.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1525581"},"PeriodicalIF":4.8000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826239/pdf/","citationCount":"0","resultStr":"{\"title\":\"Transcriptome analysis reveals the molecular mechanism of γ-linolenic acid eradicating the biofilm of vancomycin-resistant <i>Enterococcus faecium</i>.\",\"authors\":\"Ming Wei, Peng Wang, Tianmeng Li, Jun Liu, Yu Wang, Li Gu, Shuai Wang\",\"doi\":\"10.3389/fcimb.2025.1525581\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Vancomycin-resistant <i>Enterococcus faecium</i> (VRE-fm) biofilms pose a significant clinical challenge due to the limited effectiveness of traditional antibiotics. This study investigates the potential of γ-linolenic acid (GLA) as a novel antibiofilm agent.</p><p><strong>Methods: </strong>Transcriptome analysis was performed on the V27 isolate, comparing cells in mature biofilms treated with and without GLA. The findings were further validated using qRT-PCR on six VRE-fm isolates and two <i>E. faecalis</i> isolates.</p><p><strong>Results: </strong>Transcriptome analysis revealed a significant downregulation in the expression levels of genes associated with biofilm formation, including <i>fruA</i>, <i>fruB</i>, <i>sgrA</i>, <i>lpxtg-cwa</i>, <i>tfpp</i>, <i>lafA</i>, <i>lafB</i>, <i>malP</i>, <i>fsrA</i>, and <i>fsrC'</i>, while a significant upregulation was observed in the expression of <i>fsrBD</i>. Validation by qRT-PCR in six VRE-fm isolates confirmed the significant changes in the expression levels of all genes except for <i>lpxtg-cwa</i>, with statistical significance. The expression of <i>bgsB</i> and <i>bgsA</i> genes, which are the homologs of <i>lafA</i> and <i>lafB</i> genes, along with the Fsr-regulated genes <i>gelE</i> and <i>sprE</i> in <i>E. faecalis</i>, were also found to be downregulated by GLA. In addition, KEGG analysis identified specific metabolic pathways that were significantly downregulated by GLA.</p><p><strong>Conclusion: </strong>GLA effectively targets multiple aspects of biofilm formation in VRE-fm, including the downregulation of key biofilm-related genes, the inhibition of quorum sensing systems, and the modulation of metabolic pathways. GLA emerges as a promising candidate for eradicating <i>Enterococcus</i> biofilms.</p>\",\"PeriodicalId\":12458,\"journal\":{\"name\":\"Frontiers in Cellular and Infection Microbiology\",\"volume\":\"15 \",\"pages\":\"1525581\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826239/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cellular and Infection Microbiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcimb.2025.1525581\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular and Infection Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcimb.2025.1525581","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Transcriptome analysis reveals the molecular mechanism of γ-linolenic acid eradicating the biofilm of vancomycin-resistant Enterococcus faecium.
Introduction: Vancomycin-resistant Enterococcus faecium (VRE-fm) biofilms pose a significant clinical challenge due to the limited effectiveness of traditional antibiotics. This study investigates the potential of γ-linolenic acid (GLA) as a novel antibiofilm agent.
Methods: Transcriptome analysis was performed on the V27 isolate, comparing cells in mature biofilms treated with and without GLA. The findings were further validated using qRT-PCR on six VRE-fm isolates and two E. faecalis isolates.
Results: Transcriptome analysis revealed a significant downregulation in the expression levels of genes associated with biofilm formation, including fruA, fruB, sgrA, lpxtg-cwa, tfpp, lafA, lafB, malP, fsrA, and fsrC', while a significant upregulation was observed in the expression of fsrBD. Validation by qRT-PCR in six VRE-fm isolates confirmed the significant changes in the expression levels of all genes except for lpxtg-cwa, with statistical significance. The expression of bgsB and bgsA genes, which are the homologs of lafA and lafB genes, along with the Fsr-regulated genes gelE and sprE in E. faecalis, were also found to be downregulated by GLA. In addition, KEGG analysis identified specific metabolic pathways that were significantly downregulated by GLA.
Conclusion: GLA effectively targets multiple aspects of biofilm formation in VRE-fm, including the downregulation of key biofilm-related genes, the inhibition of quorum sensing systems, and the modulation of metabolic pathways. GLA emerges as a promising candidate for eradicating Enterococcus biofilms.
期刊介绍：
Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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