Expression of antimicrobial drug tolerance by attached communities of Mycobacterium tuberculosis.
Expression of antimicrobial drug tolerance by attached communities of Mycobacterium tuberculosis.
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DOI：
10.1111/2049-632x.12144
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发表时间：
2014-04
影响因子：
3.3
通讯作者：
Basaraba RJ
中科院分区：
文献类型：
--
作者：
Ackart DF;Hascall-Dove L;Caceres SM;Kirk NM;Podell BK;Melander C;Orme IM;Leid JG;Nick JA;Basaraba RJ
迫切需要改进用于筛选抗结核药物的方法。开发了一种体外试验来测试特异性靶向耐药结核分枝杆菌的药物治疗策略。H37 Rv株为M.当在含有或不含有裂解的人外周血白细胞的组织培养基（RPMI-1640）中维持时，结核菌作为附着的微生物群落在抗微生物治疗中存活。当在吐温-80存在下进行无菌培养时，杆菌未能形成微生物群落或达到对数生长期，但仍然对抗菌药物高度敏感。在没有吐温的情况下，杆菌通过形成附着于未处理的孔表面或来自裂解的人白细胞的细胞外基质的复杂微生物群落来耐受药物治疗。用DNase I或Tween处理微生物群落可有效地分散杆菌并恢复药物敏感性。这些数据表明，在体外表达的药物耐受性的M。结核病与附着的微生物群落的建立有关，并且靶向细胞外基质（包括DNA）的杆菌的分散恢复了药物敏感性。这种体外试验的改进可以证明在高通量平台中有益于筛选新的抗结核药物，特别是那些靶向耐药杆菌的抗结核药物。
There is an urgent need to improve methods used to screen anti-tuberculosis drugs. An in vitro assay was developed to test drug treatment strategies that specifically target drug-tolerant Mycobacterium tuberculosis. The H37Rv strain of M. tuberculosis survived antimicrobial treatment as attached microbial communities when maintained in tissue culture media (RPMI-1640) with or without lysed human peripheral blood leukocytes. When cultured planktonically in the presence of Tween-80, bacilli failed to form microbial communities or reach logarithmic phase growth yet remained highly susceptible to antimicrobial drugs. In the absence of Tween, bacilli tolerated drug therapy by forming complex microbial communities attached to untreated well surfaces or to the extracellular matrix derived from lysed human leukocytes. Treatment of microbial communities with DNase I or Tween effectively dispersed bacilli and restored drug susceptibility. These data demonstrate that in vitro expression of drug tolerance by M. tuberculosis is linked to the establishment of attached microbial communities and that dispersion of bacilli targeting the extracellular matrix including DNA restores drug susceptibility. Modifications of this in vitro assay may prove beneficial in a high throughput platform to screen new anti-tuberculosis drugs especially those that target drug tolerant bacilli.