National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
PLoS One. 2019 Jun 14;14(6):e0218449. doi: 10.1371/journal.pone.0218449. eCollection 2019.
Cordycepin is an efficient component of Cordyceps spp, a traditional Chinese medicine widely used for healthcare in China, and has been recently acted as a strong anticancer agent for clinic. However, whether and how it may play a role in combating tuberculosis, caused by Mycobacterium tuberculosis, remains unknown. Here we report that cordycepin can kill Mycobacterium by hijacking the bacterial adenosine kinase (AdoK), a purine salvage enzyme responsible for the phosphorylation of adenosine (Ado) to adenosine monophosphate (AMP). We show that cordycepin is a poor AdoK substrate but it competitively inhibits the catalytic activity of AdoK for adenosine phosphorylation. Cordycepin does not affect the activity of the human adenosine kinase (hAdoK), whereas hAdoK phosphorylates cordycepin to produce a new monophosphate derivative. Co-use of cordycepin and deoxycoformycin, an inhibitor of adenosine deaminase (ADD), more efficiently kills M. bovis and M. tuberculosis. The add-deleted mycobacterium is more sensitive to cordycepin. This study characterized cordycepin as a new mycobactericidal compound and also uncovered a potential anti-mycobacterial mechanism.
蛹虫草素是蛹虫草的有效成分之一，是中国传统医学中广泛用于保健的一种中药，最近也被用作一种强大的抗癌药物用于临床。然而，它是否以及如何在对抗由结核分枝杆菌引起的结核病方面发挥作用尚不清楚。在这里，我们报告蛹虫草素可以通过劫持细菌腺苷激酶（AdoK）来杀死分枝杆菌，AdoK 是一种负责将腺苷（Ado）磷酸化为单磷酸腺苷（AMP）的嘌呤补救酶。我们表明，蛹虫草素是一种较差的 AdoK 底物，但它会竞争性抑制 AdoK 对腺苷磷酸化的催化活性。蛹虫草素不影响人腺苷激酶（hAdoK）的活性，而 hAdoK 会将蛹虫草素磷酸化为产生一种新的单磷酸盐衍生物。蛹虫草素与脱氧咖啡霉素（一种腺苷脱氨酶（ADD）抑制剂）联合使用，能更有效地杀死牛分枝杆菌和结核分枝杆菌。缺少 add 的分枝杆菌对蛹虫草素更为敏感。本研究将蛹虫草素鉴定为一种新型的杀菌化合物，并揭示了一种潜在的抗分枝杆菌机制。
