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用于研究抗真菌药物活性的类人生物膜模型

Human-like Biofilm Models to Study the Activity of Antifungals Against .

作者信息

Furnica Dan-Tiberiu, Falkenstein Julia, Dittmer Silke, Steinmann Joerg, Rath Peter-Michael, Kirchhoff Lisa

机构信息

Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.

Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nürnberg, Paracelsus Medical University, 90419 Nuremberg, Germany.

出版信息

Microorganisms. 2025 Aug 31;13(9):2040. doi: 10.3390/microorganisms13092040.

DOI:10.3390/microorganisms13092040
PMID:41011372
Abstract

is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host's immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against . In both assays, metabolically active biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings.

摘要

是一种机会性丝状真菌,主要影响人体呼吸道。根据宿主的免疫反应,该病原体可导致侵袭性肺曲霉病(IPA)。形成生物膜会增加其毒力以及对抗真菌药物和免疫反应的抵抗力,是IPA发展的一个重要因素。在此,已开发出两种类人模型,即精密肺切片(PCLS)和生物膜共培养模型,以测试伏立康唑、两性霉素B以及卢立康唑对的抗生物膜活性。在这两种试验中,使用XTT试验在不同生物膜发育阶段检测代谢活跃的生物膜。在两种试验中,每种受试药物均检测到真菌生物膜代谢活性降低。在共培养模型中,对早期生物膜存在显著的抗生物膜作用。在PCLS试验中,两性霉素B在24小时后显示出最强的抑制作用。总之,所应用的PCLS体外模型可用于研究某些抗真菌化合物对生物膜的特性和活性。由于其与人体状况极为相似,PCLS模型有潜力在实验室环境中增进当前对生物膜治疗的理解。

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本文引用的文献

1
Primary cell culture systems to investigate host-pathogen interactions in bacterial respiratory tract infections of livestock.用于研究家畜细菌性呼吸道感染中宿主-病原体相互作用的原代细胞培养系统。
Front Cell Infect Microbiol. 2025 May 9;15:1565513. doi: 10.3389/fcimb.2025.1565513. eCollection 2025.
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Microbiological Non-Culture-Based Methods for Diagnosing Invasive Pulmonary Aspergillosis in ICU Patients.用于诊断重症监护病房患者侵袭性肺曲霉病的非基于培养的微生物学方法
Diagnostics (Basel). 2023 Aug 21;13(16):2718. doi: 10.3390/diagnostics13162718.
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The WHO fungal priority pathogens list as a game-changer.
世界卫生组织真菌优先病原体清单——改变游戏规则的因素。
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In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant .卢立康唑(NND-502)对唑类耐药的浮游细胞和生物被膜的体外及体内活性
J Fungi (Basel). 2022 Mar 28;8(4):350. doi: 10.3390/jof8040350.
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Eumycetoma causative agents are inhibited in vitro by luliconazole, lanoconazole and ravuconazole.球孢子菌病的病原体在体外被卢立康唑、拉夫康唑和兰康唑抑制。
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Inhibition of azole-resistant Aspergillus fumigatus biofilm at various formation stages by antifungal drugs, including olorofim.唑类耐药烟曲霉生物膜在各个形成阶段被抗真菌药物(包括奥利万星)抑制。
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PLoS Pathog. 2021 Aug 26;17(8):e1009794. doi: 10.1371/journal.ppat.1009794. eCollection 2021 Aug.
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Isolation of high-yield and -quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts.从人类精密切割肺切片中分离高产优质 RNA 用于 RNA-seq 测序,并与更大的患者队列进行计算整合。
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Fungal biofilm architecture produces hypoxic microenvironments that drive antifungal resistance.真菌生物膜结构产生低氧微环境,从而导致抗真菌耐药性。
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