School of Life Science, Anhui Province Key Laboratory of Immunology in Chronic Diseases, Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, Anhui, 233030, China.
J Microbiol. 2022 Nov;60(11):1095-1105. doi: 10.1007/s12275-022-2284-8. Epub 2022 Sep 1.
Mycobacterium tuberculosis (M. tuberculosis) is a highly pathogenic intracellular pathogen that causes tuberculosis (TB), the leading cause of mortality from single infections. Redox homeostasis plays a very important role in the resistance of M. tuberculosis to antibiotic damage and various environmental stresses. The antioxidant sulforaphane (SFN) has been reported to exhibit anticancer activity and inhibit the growth of a variety of bacteria and fungi. Nonetheless, it remains unclear whether SFN exhibits anti-mycobacterial activity. Our results showed that the SFN against M. tuberculosis H37Ra exhibited bactericidal activity in a time and dose-dependent manner. The anti-tubercular activity of SFN was significantly correlated with bacterial reactive oxygen species (ROS) levels. In addition, SFN promoted the bactericidal effect of macrophages on intracellular bacteria in a dose-dependent manner, mediated by increasing intracellular mitochondrial ROS levels and decreasing cytoplasmic ROS levels. Taken together, our data revealed the previously unrecognized antimicrobial functions of SFN. Future studies focusing on the mechanism of SFN in macrophages against M. tuberculosis are essential for developing new host-directed therapeutic approaches against TB.
结核分枝杆菌(Mycobacterium tuberculosis,M. tuberculosis)是一种高度致病性的细胞内病原体,可引起结核病(tuberculosis,TB),这是单一感染导致死亡的主要原因。氧化还原稳态在结核分枝杆菌对抗抗生素损伤和各种环境压力的抗性中起着非常重要的作用。抗氧化剂萝卜硫素(sulforaphane,SFN)已被报道具有抗癌活性,并抑制多种细菌和真菌的生长。然而,SFN 是否具有抗分枝杆菌活性仍不清楚。我们的结果表明,SFN 对 H37Ra 结核分枝杆菌具有时间和剂量依赖性的杀菌活性。SFN 的抗结核活性与细菌活性氧(reactive oxygen species,ROS)水平显著相关。此外,SFN 以剂量依赖的方式促进巨噬细胞对细胞内细菌的杀菌作用,这是通过增加细胞内线粒体 ROS 水平和降低细胞质 ROS 水平来介导的。综上所述,我们的数据揭示了 SFN 以前未被认识到的抗菌功能。未来的研究集中在 SFN 在巨噬细胞中针对结核分枝杆菌的作用机制上,对于开发针对结核病的新的宿主导向治疗方法至关重要。