Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Hachinohe College of Technology, Aomori, 039-1192, Japan.
J Antibiot (Tokyo). 2024 Jun;77(6):353-364. doi: 10.1038/s41429-024-00716-4. Epub 2024 Mar 25.
The antimicrobial activity of tumescenamide C against the scab-forming S. scabiei NBRC13768 was confirmed with a potent IC value (1.5 μg/mL). Three tumescenamide C-resistant S. scabiei strains were generated to compare their gene variants. All three resistant strains contained nonsynonymous variants in genes related to cellobiose/cellotriose transport system components; cebF1, cebF2, and cebG2, which are responsible for the production of the phytotoxin thaxtomin A. Decrease in thaxtomin A production and the virulence of the three resistant strains were revealed by the LC/MS analysis and necrosis assay, respectively. Although the nonsynonymous variants were insufficient for identifying the molecular target of tumescenamide C, the cell wall component wall teichoic acid (WTA) was observed to bind significantly to tumescenamide C. Moreover, changes in the WTA contents were detected in the tumescenamide C-resistant strains. These results imply that tumescenamide C targets the cell wall system to exert antimicrobial effects on S. scabiei.
抑霉胺 C 对形成结痂的 S. scabiei NBRC13768 的抗微生物活性得到了确认,其 IC 值(1.5μg/mL)非常有效。为了比较基因变异,生成了三种抑霉胺 C 抗性的 S. scabiei 菌株。所有三种抗性菌株的细胞二糖/纤维三糖转运系统成分相关基因 cebF1、cebF2 和 cebG2 中都存在非同义变异,这些基因负责产生植物毒素噻枯菌素 A。通过 LC/MS 分析和坏死测定分别揭示了三种抗性菌株中噻枯菌素 A 产量和毒力的降低。尽管非同义变异不足以确定抑霉胺 C 的分子靶标,但观察到细胞壁成分壁磷壁酸 (WTA) 与抑霉胺 C 结合显著。此外,在抑霉胺 C 抗性菌株中检测到 WTA 含量的变化。这些结果表明,抑霉胺 C 靶向细胞壁系统对 S. scabiei 发挥抗微生物作用。