In vitro effects of antimicrobial agents on Mycobacterium leprae in mouse peritoneal macrophages.
In vitro effects of antimicrobial agents on Mycobacterium leprae in mouse peritoneal macrophages.
复制标题
抗菌药物对小鼠腹膜巨噬细胞中麻风分枝杆菌的体外影响。
DOI：
10.1128/aac.33.5.657
复制
发表时间：
1989
影响因子：
4.9
通讯作者：
Hastings,RC
中科院分区：
文献类型：
--
作者：
Ramasesh,N;Krahenbuhl,JL;Hastings,RC
麻风分枝杆菌在体内合成大量的特定的含邻苯二甲酸酯的酚糖脂。我们已经证明了可行的M。麻风病人在体外培养的巨噬细胞中很容易将放射性标记的棕榈酸掺入酚糖脂I中，这一过程被抗麻风药物利福平抑制。在本文中，我们报告了应用这一观察，以快速评价超过25种抗菌药物的潜在抗麻风活性在体外。所有已知的抗麻风药物利福平，氨苯砜，氯法齐明，乙硫异烟胺抑制酚糖脂I的合成。利福霉素的螺哌啶基衍生物利福沙星也报告在小鼠模型中具有活性，非常有效。有趣的是，大环内酯类红霉素、克拉霉素和罗红霉素也被发现在该系统中具有活性，而D-环丝氨酸和其他细胞壁合成抑制剂没有显示出效果。许多在该系统中发现有活性的化合物已被报道在小鼠体内有效。这种相关性支持的可行性，使用酚糖脂I合成的快速评价抗麻风病的新药。
Mycobacterium leprae synthesizes large quantities of a specific phthiocerol-containing phenolic glycolipid in vivo. We have shown earlier that viable M. leprae readily incorporates radiolabeled palmitic acid into phenolic glycolipid I when residing in cultured macrophages in vitro and that this process is inhibited by the antileprosy drug rifampin. In the present paper we report that application of this observation to the rapid evaluation of over 25 antimicrobial agents for potential antileprosy activity in vitro. All the known antileprosy drugs rifampin, dapsone, clofazimine, and ethionamide inhibited phenolic glycolipid I synthesis. Rifabutin, a spiropiperidyl derivative of rifamycin, also reported to be active in the mouse model, was very effective. Interestingly, the macrolides erythromycin, clarithromycin, and roxithromycin were also found to be active in this system, while D-cycloserine and other cell wall synthesis inhibitors showed no effect. Many of the compounds found to be active in this system have been reported to be effective in vivo in mice. This correlation lends support to the feasibility of using phenolic glycolipid I synthesis for the rapid evaluation of new drugs against leprosy.