Zeng Zixian, Cao Wei, Pu Hong, Wu Dousheng, Jiang Sai, Su Meng, Wang Yajing, Wang Zhi, Zhao Xin, Li Juan, Li Shunxiang, Jiang Lin
Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
Department of Pharmacy, Hunan Children's Hospital, Changsha 410007, China.
Pestic Biochem Physiol. 2025 Sep;213:106517. doi: 10.1016/j.pestbp.2025.106517. Epub 2025 Jun 26.
Bacterial wilt, caused by the soil-borne phytopathogen Ralstonia solanacearum (R. solanacearum), poses a serious threat to global agriculture. In this study, 26 actinomycete strains were isolated from the rhizosphere of traditional Chinese medicinal plants. Among them, Streptomyces sp. JL2001 exhibited strong inhibitory activity against R. solanacearum both in vitro and in planta. UPLC-QTOF-MS/MS analysis identified aerugine as the major active compound, alongside five structurally related 2-hydroxyphenylthiazoline derivatives. Chemically synthesized aerugine showed broad-spectrum antibacterial activity, significantly inhibiting planktonic growth and biofilm formation and alleviating bacterial wilt symptoms in tomato seedlings under hydroponic and soil-based conditions. Mechanistically, aerugine disrupts bacterial membranes, interferes with lipid metabolism, and downregulates key virulence systems, including flagellar assembly and the type III secretion system. These findings were supported by electron microscopy, proteomic profiling, and qPCR validation. Whole-genome sequencing of JL2001 revealed a 7.75 Mb chromosome containing 22 biosynthetic gene clusters (BGCs), including a thiazostatin-like NRPS-dependent BGC likely responsible for aerugine biosynthesis. Importantly, soil-based assays demonstrated that aerugine significantly and dose-dependently suppressed R. solanacearum in natural soil, while also inducing changes in microbial composition. Later-stage increases in bacterial abundance and diversity, particularly of morphologically distinct non-pathogenic colonies, suggest that aerugine not only eliminates pathogens but may also promote beneficial microbiota -a dual protection mechanism. This study highlights Streptomyces sp. JL2001 and aerugine as promising agents for the sustainable control of bacterial wilt and provides new insights into their molecular antibacterial mechanisms.
青枯病由土壤传播的植物病原菌青枯雷尔氏菌（Ralstonia solanacearum）引起，对全球农业构成严重威胁。在本研究中，从传统中药材根际分离出26株放线菌菌株。其中，链霉菌属JL2001菌株在体外和植物体内均对青枯雷尔氏菌表现出强大的抑制活性。超高效液相色谱-四极杆飞行时间串联质谱（UPLC-QTOF-MS/MS）分析确定，铜绿菌素是主要活性化合物，同时还有5种结构相关的2-羟基苯基噻唑啉衍生物。化学合成的铜绿菌素表现出广谱抗菌活性，能显著抑制浮游生长和生物膜形成，并缓解水培和土培条件下番茄幼苗的青枯病症状。从机制上讲，铜绿菌素破坏细菌细胞膜，干扰脂质代谢，并下调包括鞭毛组装和III型分泌系统在内的关键毒力系统。这些发现得到了电子显微镜、蛋白质组分析和定量聚合酶链反应（qPCR）验证的支持。JL2001的全基因组测序显示，其染色体大小为7.75 Mb，包含22个生物合成基因簇（BGC），其中一个类似硫链丝菌素的非核糖体肽合成酶（NRPS）依赖性BGC可能负责铜绿菌素的生物合成。重要的是，土培试验表明，铜绿菌素能在天然土壤中显著且剂量依赖性地抑制青枯雷尔氏菌，同时还能引起微生物组成的变化。后期细菌丰度和多样性的增加，特别是形态上不同的非致病菌落的增加，表明铜绿菌素不仅能消除病原体，还可能促进有益微生物群——一种双重保护机制。本研究强调链霉菌属JL2001菌株和铜绿菌素是可持续防治青枯病的有前景的药剂，并为它们的分子抗菌机制提供了新见解。
