Temporal and intrinsic factors of rifampicin tolerance in mycobacteria
Temporal and intrinsic factors of rifampicin tolerance in mycobacteria
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DOI：
10.1073/pnas.1600372113
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发表时间：
2016-07-19
影响因子：
11.1
通讯作者：
Aldridge, Bree B.
中科院分区：
文献类型：
--
作者：
Richardson, Kirill;Bennion, Owen T.;Aldridge, Bree B.
分枝杆菌不对称地生长和分裂，造成生长极年龄、生长特性和抗生素敏感性的变异性。在这里，我们研究了生长极年龄和其他生长特性在确定污垢分枝杆菌对利福平挑战的反应谱中的重要性。我们使用活细胞显微镜和建模相结合的方法来前瞻性地识别利福平敏感性改变的亚群。我们发现有两个亚群的易感性增加。在治疗开始时，敏感细胞要么很小，处于细胞周期的早期阶段，要么很大，处于细胞周期的后期阶段。与这种易感性的时间窗口相反，耐受性与分裂时遗传的因素有关：较长的出生长度和成熟的生长极。因此，利福平的反应是复杂的，这是由于不对称分裂和相对于细胞出生的治疗时机所建立的差异的组合。
Mycobacteria grow and divide asymmetrically, creating variability in growth pole age, growth properties, and antibiotic susceptibilities. Here, we investigate the importance of growth pole age and other growth properties in determining the spectrum of responses of Mycobacterium smegmatis to challenge with rifampicin. We used a combination of live-cell microscopy and modeling to prospectively identify subpopulations with altered rifampicin susceptibility. We found two subpopulations that had increased susceptibility. At the initiation of treatment, susceptible cells were either small and at early stages of the cell cycle, or large and in later stages of their cell cycle. In contrast to this temporal window of susceptibility, tolerance was associated with factors inherited at division: long birth length and mature growth poles. Thus, rifampicin response is complex and due to a combination of differences established from both asymmetric division and the timing of treatment relative to cell birth.