Bie Pengfei, Yang Xiaowen, Zhang Cunrui, Wu Qingmin
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Front Microbiol. 2020 Jan 21;10:2936. doi: 10.3389/fmicb.2019.02936. eCollection 2019.
Brucellosis, caused by intracellular gram-negative pathogens of the genus , continues to be one of the most pandemic zoonotic diseases in most countries. At present, the therapeutic treatment of brucellosis relies on a combination of multiple antibiotics that involves a long course of treatment, easy relapse, and high side effects from the use of certain antibiotics (such as streptomycin). Thus, the need to identify novel drugs or targets to control this disease is urgent. Diaminopimelate decarboxylase (DAPDC), a key enzyme involved in the bacterial diaminopimelate (DAP) biosynthetic pathway, was suggested to be a promising anti- target in our previous study. In this work, the biological activity of DAPDC was characterized, and a library of 1,591 compounds was screened for inhibitors of DAPDC. The results of a high-throughput screening (HTS) assay showed that 24 compounds inhibited DAPDC activity. In a further bacterial inhibition experiment, five compounds exhibited anti- activity (SID3, SID4, SID14, SID15, and SID20). These results suggested that the identified compounds can be used as potent molecules against brucellosis and that the application ranges of these approved drugs can be expanded in the future.
布鲁氏菌病由布鲁氏菌属细胞内革兰氏阴性病原体引起，在大多数国家仍然是最具流行性的人畜共患病之一。目前，布鲁氏菌病的治疗依赖于多种抗生素联合使用，疗程长、易复发，且某些抗生素（如链霉素）副作用大。因此，迫切需要鉴定控制这种疾病的新药或靶点。二氨基庚二酸脱羧酶（DAPDC）是细菌二氨基庚二酸（DAP）生物合成途径中的关键酶，在我们之前的研究中被认为是一个有前景的抗布鲁氏菌靶点。在这项工作中，对DAPDC的生物学活性进行了表征，并筛选了一个包含1591种化合物的文库以寻找DAPDC抑制剂。高通量筛选（HTS）试验结果表明，有24种化合物抑制了DAPDC活性。在进一步的细菌抑制实验中，有5种化合物表现出抗布鲁氏菌活性（SID3、SID4、SID14、SID15和SID20）。这些结果表明，所鉴定的化合物可作为抗布鲁氏菌病的有效分子，并且这些已批准药物的应用范围在未来可能会扩大。
