Deferiprone inhibits virulence and biofilm formation in Burkholderia cenocepacia.

IF 5.5 3区医学 Q1 IMMUNOLOGY

Medical Microbiology and Immunology Pub Date : 2025-03-08 DOI:10.1007/s00430-025-00824-4

Zhi-Wen Ding, Kai-Zhong Xu, Owias Iqbal Dar, Lu-Jun Yin, Ying-Jie Wang, Yun-Tong Liao, Peng Wang, Ai-Qun Jia

{"title":"Deferiprone inhibits virulence and biofilm formation in Burkholderia cenocepacia.","authors":"Zhi-Wen Ding, Kai-Zhong Xu, Owias Iqbal Dar, Lu-Jun Yin, Ying-Jie Wang, Yun-Tong Liao, Peng Wang, Ai-Qun Jia","doi":"10.1007/s00430-025-00824-4","DOIUrl":null,"url":null,"abstract":"<p><p>Burkholderia cenocepacia, an opportunistic pathogen, poses a significant threat to human health, necessitating the discovery of effective quorum sensing inhibitors (QSIs). In this study, the quorum sensing inhibitory effects of deferiprone (DFP) on the B. cenocepacia 162,638 were validated. Notably, DFP demonstrated an ability to inhibit and disrupt bacterial biofilms, reducing biofilm formation by 44.59% at 1/4 MIC (minimum inhibitory concentration) and 24.32% at 1/8 MIC concentrations. The study also investigated DFP's impact on motility, virulence, and QS signal levels. LC-MS/MS analysis showed a gradual reduction in the QS molecule C6-HSL as DFP concentrations increased. Additionally, DFP's non-hemolytic properties and safety profile, as verified in Galleria mellonella infection models, highlighted its biocompatibility. RT-qPCR results further indicated that DFP downregulated QS-related gene expression, particularly those involved in ferric uptake regulation protein (Fur). Molecular docking studies identified Fur as a key target for DFP's inhibitory action. Collectively, DFP was shown as a potential QSI with practical applications for controlling B. cenocepacia infections.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"15"},"PeriodicalIF":5.5000,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Microbiology and Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00430-025-00824-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Burkholderia cenocepacia, an opportunistic pathogen, poses a significant threat to human health, necessitating the discovery of effective quorum sensing inhibitors (QSIs). In this study, the quorum sensing inhibitory effects of deferiprone (DFP) on the B. cenocepacia 162,638 were validated. Notably, DFP demonstrated an ability to inhibit and disrupt bacterial biofilms, reducing biofilm formation by 44.59% at 1/4 MIC (minimum inhibitory concentration) and 24.32% at 1/8 MIC concentrations. The study also investigated DFP's impact on motility, virulence, and QS signal levels. LC-MS/MS analysis showed a gradual reduction in the QS molecule C6-HSL as DFP concentrations increased. Additionally, DFP's non-hemolytic properties and safety profile, as verified in Galleria mellonella infection models, highlighted its biocompatibility. RT-qPCR results further indicated that DFP downregulated QS-related gene expression, particularly those involved in ferric uptake regulation protein (Fur). Molecular docking studies identified Fur as a key target for DFP's inhibitory action. Collectively, DFP was shown as a potential QSI with practical applications for controlling B. cenocepacia infections.

查看原文本刊更多论文

去铁素抑制伯克霍尔德菌毒力和生物膜形成。

新绿伯克霍尔德菌是一种机会致病菌，对人类健康构成重大威胁，需要发现有效的群体感应抑制剂（qsi）。本研究验证了去铁素（DFP）对青霉162638的群体感应抑制作用。值得注意的是，DFP显示出抑制和破坏细菌生物膜的能力，在1/4 MIC（最低抑制浓度）下减少44.59%的生物膜形成，在1/8 MIC浓度下减少24.32%。该研究还调查了DFP对运动性、毒力和QS信号水平的影响。LC-MS/MS分析显示，随着DFP浓度的增加，QS分子C6-HSL逐渐减少。此外，在mellonella Galleria感染模型中验证的DFP的非溶血特性和安全性突出了其生物相容性。RT-qPCR结果进一步表明，DFP下调了qs相关基因的表达，尤其是铁摄取调节蛋白（Fur）相关基因的表达。分子对接研究发现Fur是DFP抑制作用的关键靶点。总的来说，DFP被证明是一种潜在的QSI，具有控制结核杆菌感染的实际应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Medical Microbiology and Immunology 医学-免疫学

CiteScore

10.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.