ProcCluster® 和盐酸普鲁卡因可抑制曲霉菌的生长,并在体外与甲型流感病毒和烟曲霉菌共同感染时发挥抗菌作用。

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-10-15 eCollection Date: 2024-01-01 DOI:10.3389/fcimb.2024.1445428
Sarah König, Josefine Schroeder, Thorsten Heinekamp, Axel A Brakhage, Bettina Löffler, Beatrice Engert, Christina Ehrhardt
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引用次数: 0

摘要

导言:流感相关肺曲霉菌病死亡率高,治疗方案有限。目前的标准做法是分别治疗每种病原体。然而,抗真菌药物的使用可能会导致严重的副作用,三唑类抗药性曲霉菌株的存在也会使抗真菌治疗复杂化。此外,抗药性流感病毒也越来越受到临床关注。一种能影响真菌和病毒繁殖的药物可以克服这些缺点。因此,我们研究了 ProcCluster® 和盐酸普鲁卡因 (HCl) 的抗真菌和抗病毒特性:方法:在人类无细胞系统中,用试验物质处理不同烟曲霉菌株、黄曲霉菌株和赤霉菌株的分生孢子,并通过荧光显微镜或吸收测量分析其抗真菌特性。使用荧光显微镜观察了用 ProcCluster® 处理烟曲霉过程中代谢活性和细胞内 Ca2+ 分布的变化。此外,在肺上皮细胞体外同时感染烟曲霉菌和甲型流感病毒(IAV)的过程中,研究了 ProcCluster® 和普鲁卡因盐酸盐的抗真菌和抗病毒特性。分析方法包括荧光显微镜、标准斑块检测和 Western 印迹检测:结果:这两种物质都能抑制真菌的生长,即使在真菌发芽后或有纯化的 IAV 颗粒存在时使用也是如此。ProcCluster® 对抗三唑的烟曲霉菌株仍然有效。但是,加入 CaCl2 后,抗真菌效果会发生逆转,这表明 ProcCluster® 通过破坏真菌的 Ca2+ 稳态来抑制真菌生长。此外,体外研究表明,ProcCluster® 和盐酸普鲁卡因能减少 IAV 和烟曲霉共同感染时的病原体负荷。最后,ProcCluster®与抗病毒药物法非拉韦(favipiravir)的联合使用显示出更强的抗病原活性,尤其是对IAV复制的抗病原活性:本研究强调了 ProcCluster® 和盐酸普鲁卡因作为抗感染物质对各种病原体的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ProcCluster® and procaine hydrochloride inhibit the growth of Aspergillus species and exert antimicrobial properties during coinfection with influenza A viruses and A. fumigatus in vitro.

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine.

Methods: Conidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay.

Results: Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication.

Discussion: This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens.

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来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
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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