利用耻垢分枝杆菌作为替代物来评估抗结核分枝杆菌药物先导化合物。
Application of Mycobacterium smegmatis as a surrogate to evaluate drug leads against Mycobacterium tuberculosis.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN, 38163, USA.
Department of Veterinary and Biomedical Sciences, University of Minnesota, 205 VSB, 1971 Commonwealth Avenue, St. Paul, MN, 55108, USA.
出版信息
J Antibiot (Tokyo). 2020 Nov;73(11):780-789. doi: 10.1038/s41429-020-0320-7. Epub 2020 May 29.
Discovery of new anti-tuberculosis (TB) drugs is a time-consuming process due to the slow-growing nature of Mycobacterium tuberculosis (Mtb). A requirement of biosafety level 3 (BSL-3) facility for performing research associated with Mtb is another limitation for the development of TB drug discovery. In our screening of BSL-1 Mycobacterium spp. against a battery of TB drugs, M. smegmatis (ATCC607) exhibits good agreement with its drug susceptibility against the TB drugs under a low-nutrient culture medium (0.5% Tween 80 in Middlebrook 7H9 broth). M. smegmatis (ATCC607) enters its dormant form in 14 days under a nutrient-deficient condition (a PBS buffer), and shows resistance to a majority of TB drugs, but shows susceptibility to amikacin, capreomycin, ethambutol, and rifampicin (with high concentrations) whose activities against non-replicating (or dormant) Mtb were previously validated.
由于结核分枝杆菌（Mycobacterium tuberculosis，Mtb）的生长缓慢，因此发现新的抗结核（TB）药物是一个耗时的过程。进行与 Mtb 相关的研究需要生物安全 3 级（BSL-3）设施，这也是开发 TB 药物发现的另一个限制因素。在我们对 BSL-1 分枝杆菌属进行的针对一系列 TB 药物的筛选中，耻垢分枝杆菌（ATCC607）在低营养培养基（Middlebrook 7H9 肉汤中的 0.5%Tween 80）中对 TB 药物的药敏性与实际情况非常吻合。在营养缺乏的条件下（PBS 缓冲液），耻垢分枝杆菌（ATCC607）在 14 天内进入休眠状态，并对大多数 TB 药物表现出耐药性，但对阿米卡星、卷曲霉素、乙胺丁醇和利福平（高浓度）表现出敏感性，这些药物的抗非复制（或休眠）Mtb 活性先前已得到验证。
Zotero 插件