Ji Ying, Han Ji, Moses Munika, Wang Di, Wu Lei, Xue Wenwen, Sun Lu, Xu Bo, Chen Changbin, Xiang Yanwei, Huang Xinhua
Unit of Pathogenic Fungal Infection & Host Immunity, CAS Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, China.
Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164 Lanxi Road, Shanghai, 200062, China.
Microb Pathog. 2024 Apr;189:106573. doi: 10.1016/j.micpath.2024.106573. Epub 2024 Feb 13.
The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.
由新型、突发和耐药病原体引起的感染大幅增加，对人类健康构成重大威胁。虽然众多研究已证明中药的抗菌和抗病毒作用，但具有广谱抗菌特性的中药复方混合物的潜力仍未得到充分探索。本研究旨在开发一种中药复方混合物JY-1，并研究其抗菌特性及其对致病微生物的潜在作用机制。使用抑菌圈试验和点滴平板法评估抗菌活性。使用含10%胎牛血清的RPMI1640培养基诱导白色念珠菌形成菌丝，随后进行显微镜观察。采用定量实时PCR（RT-qPCR）定量菌丝特异性基因如HWP1和ALS3的转录水平。使用XTT还原试验和扫描电子显微镜（SEM）评估JY-1对生物膜形成的影响。此外，通过蛋白质和核酸泄漏试验评估细胞膜完整性。我们的结果清楚地表明，JY-1显著抑制念珠菌属和隐球菌属的营养生长。此外，这种复方混合物对多种病原菌有效，包括金黄色葡萄球菌、耐万古霉素肠球菌、大肠杆菌、肺炎克雷伯菌和阴沟肠杆菌。更有趣的是，JY-1对哺乳动物病毒病原体水疱性口炎病毒（VSV）具有直接抗病毒作用。进一步的机制研究表明，JY-1可降低菌丝特异性基因HWP1和ALS3的表达，从而抑制白色念珠菌的菌丝形成。JY-1的抗菌特性可归因于其减少生物膜形成和破坏细胞膜通透性的能力，这一过程导致微生物细胞死亡并释放细胞内容物。综上所述，我们的研究鉴定出一种强效的广谱抗菌剂，一种中药复方混合物，可能被开发为一种潜在的抗菌药物。
