Yang Chunxi, Cui Chaoyu, Chen Yanru, Peng Zimei
Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
Jiangxi Key Laboratory for Excavation and Utilization of Agricultural Microorganisms, Jiangxi Agricultural University, Nanchang, China.
Front Cell Infect Microbiol. 2025 Sep 2;15:1515537. doi: 10.3389/fcimb.2025.1515537. eCollection 2025.
, known as the "super fungus", is commonly existed in hospital. The treatment of infection is difficult for its multi-drug resistance and difficult to accurately detect. The use of synthetic antibacterial agents has caused major problems such as drug-resistance and environment pollution and negatively affects non-target species. Microbial biocontrol agents (probiotics) are needed for fungal infection. and related genera produce a variety of bioactive substances. As probiotics, it has been widely studied in the field of medicine and is a novel microbial factor for biological control.
NC-B4 was isolated using gradient dilution method. Then it was identified by phylogenetic analysis and physiological and biochemical characteristics. The antibacterial mechanism of NC-B4 was explored by detecting cellulase, protease and genomic analysis. Then antimicrobial effects were analyzed by detecting the growth and biofilm of BJCA001. Finally, the cytotoxicity and the protective effect on mice were analyzed by cell line and mouse systemic infection models.
We isolated NC-B4, which showed cellulase, protease enzyme activity and antimicrobial effects against human pathogenic fungi by inhibiting the growth of Candida auris, and mycelial fungus. NC-B4 inhibited the biofilm formation and growth of C. auris. NC-B4 has a protective effect against the toxicity of Candida auris in A549 cell line and mouse systemic infection models. The complete genome of NC-B4 was 3.93 Mb with a 46.5% G+C content and possessed the macrolactin H, bacillaene, fengycin, difficidin, bacillibactin and bacilysin biosynthesis cluster, which known as key factors in biological control.
The results of the present study indicated that NC-B4 has antimicrobial properties for its cellulase, protease and antibacterial secondary metabolites, thereby inhibiting the growth of pathogenic bacteria and the formation of biofilms. NC-B4 is expected to be developed as a source for probiotics or new antibiotics.
耳念珠菌,被称为“超级真菌”,在医院中普遍存在。由于其多重耐药性以及难以准确检测,耳念珠菌感染的治疗颇具难度。合成抗菌剂的使用引发了诸如耐药性和环境污染等重大问题,并对非目标物种产生负面影响。真菌感染需要微生物生物防治剂(益生菌)。芽孢杆菌属及相关属产生多种生物活性物质。作为益生菌,它在医学领域已得到广泛研究,是一种用于生物防治的新型微生物因子。
采用梯度稀释法分离出NC - B4。然后通过系统发育分析以及生理生化特征对其进行鉴定。通过检测纤维素酶、蛋白酶以及基因组分析来探究NC - B4的抗菌机制。接着通过检测耳念珠菌BJCA001的生长和生物膜来分析抗菌效果。最后通过细胞系和小鼠全身感染模型分析细胞毒性以及对小鼠的保护作用。
我们分离出了NC - B4,它表现出纤维素酶、蛋白酶活性以及对人类致病真菌的抗菌作用,通过抑制耳念珠菌、白色念珠菌和丝状真菌的生长来实现。NC - B4抑制了耳念珠菌生物膜的形成和生长。NC - B4在A549细胞系和小鼠全身感染模型中对耳念珠菌的毒性具有保护作用。NC - B4的完整基因组为3.93 Mb,G + C含量为46.5%,并拥有大环内酯素H、杆菌烯、丰原素、艰难梭菌素、杆菌铁载体和杆菌溶素生物合成簇,这些被认为是生物防治的关键因素。
本研究结果表明,NC - B4因其纤维素酶、蛋白酶和抗菌次级代谢产物而具有抗菌特性,从而抑制病原菌的生长和生物膜的形成。NC - B4有望被开发成为益生菌或新型抗生素的来源。