Wen Zewen, Wang Cong, Bai Bing, Cao Xinyi, Fan Kewei, Hu Chunyou, Li Peiyu, Deng Qiwen, Yu Zhijian
Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89 Taoyuan Road, Nanshan District, Shenzhen 518052, China.
Department of Microbiology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154003, China.
ACS Infect Dis. 2023 Oct 13;9(10):1867-1877. doi: 10.1021/acsinfecdis.3c00188. Epub 2023 Sep 11.
is the major cause of invasive neonatal infections and is a recognized pathogen associated with various diseases in nonpregnant adults. The emergence and spread of antibiotic-resistant necessitate the development of a novel antibacterial agent. Here, the potential antibacterial activities and mechanisms of ginkgolic acid C15:1 (GA (15:1)) from against clinical are characterized. The MIC and MIC values for GA (15:1) against 72 clinical isolates were 6.25 and 12.5 μM, respectively. GA (15:1) showed a strong bactericidal effect against both planktonic bacteria and bacteria embedded in biofilms as well as significant effectiveness in suppressing the growth of biofilms. Moreover, GA (15:1) possesses intracellular antibacterial activity and could significantly decrease the bacterial burden in the intraperitoneal infection model of . Mechanistic studies showed that GA (15:1) triggers membrane damage of S. agalactiae through a unique dual-targeting mechanism of action (MoA). First, GA (15:1) targets phospholipids in the bacterial cytoplasmic membrane. Second, by using mass-spectrometry-based drug affinity responsive target stability (DARTS) and molecular docking, lipoprotein signaling peptidase II (lspA) was identified as a target protein of GA (15:1), whose role is crucial for maintaining bacterial membrane depolarization and permeabilization. Our findings suggest a potential therapeutic strategy for developing GA (15:1) to combat infections.
是侵袭性新生儿感染的主要原因，也是一种与非妊娠成人各种疾病相关的公认病原体。抗生素耐药性的出现和传播使得新型抗菌剂的研发成为必要。在此，对来自银杏的银杏酸C15:1（GA(15:1)）针对临床分离株的潜在抗菌活性和作用机制进行了表征。GA(15:1)对72株临床分离株的MIC和MIC值分别为6.25和12.5μM。GA(15:1)对浮游细菌和生物膜中嵌入的细菌均显示出强大的杀菌作用，并且在抑制生物膜生长方面具有显著效果。此外，GA(15:1)具有细胞内抗菌活性，并且在动物腹腔感染模型中可显著降低细菌载量。机制研究表明，GA(15:1)通过独特的双靶点作用机制引发无乳链球菌的膜损伤。首先，GA(15:1)靶向细菌细胞质膜中的磷脂。其次，通过基于质谱的药物亲和响应靶点稳定性（DARTS）和分子对接，脂蛋白信号肽酶II（lspA）被鉴定为GA(15:1)的靶点蛋白，其作用对于维持细菌膜去极化和通透性至关重要。我们的研究结果提示了开发GA(15:1)对抗感染的潜在治疗策略。 （注：原文中部分关键细菌名称未明确写出，翻译时保留英文）
