The potential application of isoxanthohumol in inhibiting Clostridium perfringens infection by targeting the type IV pili.

IF 4.9 2区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Microbial Cell Factories Pub Date : 2025-02-21 DOI:10.1186/s12934-025-02644-w

Zeyu Song, Yanhong Deng, Jichuan Zhang, Zhongmei Wen, Shui Liu, Xuming Deng, Qiaoling Zhang, Qianghua Lv

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Abstract

Background: Clostridium perfringens (C. perfringens) is an important zoonotic pathogen. The diseases such as necrotic enteritis (NE), enterotoxemia, gas gangrene and food poisoning caused by its infection seriously threaten the lives of both humans and animals. However, under the severe situation of antibiotic resistance, the development of new antibacterial strategies or drugs deserves great attention.

Results: In this study, we selected the virulence factor Type IV pili (TFP) of C. perfringens as the target for drug screening. The gliding motility, biofilm formation, cell adhesion and antibacterial activity of the natural compound isoxanthohumol (IXN) against C. perfringens were determined. Transmission electron microscopy (TEM), TFP gene transcription analysis and Western blot were used to detect the expression of PilA pilin. The therapeutic effect of IXN on C. perfringens infection was demonstrated through a mouse gas gangrene model. It was confirmed that IXN inhibits the function of TFP by down-regulating TFP-encoding genes and two-component regulatory genes.

Conclusions: In conclusion, our study shows that IXN has the potential to inhibit the function of TFP in C. perfringens and for anti-infection applications.

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异黄腐酚靶向IV型菌毛抑制产气荚膜梭菌感染的潜在应用。

背景：产气荚膜梭菌是一种重要的人畜共患病原体。其感染引起的坏死性肠炎、肠毒血症、气性坏疽和食物中毒等疾病严重威胁着人类和动物的生命。然而，在抗生素耐药性严重的情况下，开发新的抗菌策略或药物值得高度重视。结果：本研究选择产气荚膜梭菌的毒力因子IV型菌毛（TFP）作为药物筛选的靶点。测定了天然化合物异黄腐酚（IXN）对产气荚膜梭菌的滑行动力、生物膜形成、细胞粘附及抑菌活性。采用透射电镜（TEM）、TFP基因转录分析和Western blot检测PilA pilin的表达。通过小鼠气性坏疽模型验证了IXN对产气荚膜梭菌感染的治疗作用。证实IXN通过下调TFP编码基因和双组分调控基因抑制TFP功能。结论：综上所述，本研究表明IXN具有抑制产气荚膜梭菌TFP的功能和抗感染的潜力。

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来源期刊

Microbial Cell Factories 工程技术-生物工程与应用微生物

CiteScore

9.30

自引率

4.70%

发文量

235

审稿时长

2.3 months

期刊介绍： Microbial Cell Factories is an open access peer-reviewed journal that covers any topic related to the development, use and investigation of microbial cells as producers of recombinant proteins and natural products, or as catalyzers of biological transformations of industrial interest. Microbial Cell Factories is the world leading, primary research journal fully focusing on Applied Microbiology. The journal is divided into the following editorial sections: -Metabolic engineering -Synthetic biology -Whole-cell biocatalysis -Microbial regulations -Recombinant protein production/bioprocessing -Production of natural compounds -Systems biology of cell factories -Microbial production processes -Cell-free systems