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Single-cell imaging of the Mycobacterium tuberculosis cell cycle reveals linear and heterogenous growth
Nature Microbiology ( IF 20.5 ) Pub Date : 2024-11-15 , DOI: 10.1038/s41564-024-01846-z
Eun Seon Chung, Prathitha Kar, Maliwan Kamkaew, Ariel Amir, Bree B. Aldridge

Difficulties in antibiotic treatment of Mycobacterium tuberculosis (Mtb) are partly thought to be due to heterogeneity in growth. Although the ability of bacterial pathogens to regulate growth is crucial to control homeostasis, virulence and drug responses, single-cell growth and cell cycle behaviours of Mtb are poorly characterized. Here we use time-lapse, single-cell imaging of Mtb coupled with mathematical modelling to observe asymmetric growth and heterogeneity in cell size, interdivision time and elongation speed. We find that, contrary to Mycobacterium smegmatis, Mtb initiates cell growth not only from the old pole but also from new poles or both poles. Whereas most organisms grow exponentially at the single-cell level, Mtb has a linear growth mode. Our data show that the growth behaviour of Mtb diverges from that of model bacteria, provide details into how Mtb grows and creates heterogeneity and suggest that growth regulation may also diverge from that in other bacteria.



中文翻译:


结核分枝杆菌细胞周期的单细胞成像显示线性和异质性生长



结核分枝杆菌 (Mtb) 抗生素治疗困难部分被认为是由于生长的异质性。尽管细菌病原体调节生长的能力对于控制稳态、毒力和药物反应至关重要,但 Mtb 的单细胞生长和细胞周期行为表征不佳。在这里,我们使用 Mtb 的延时、单细胞成像与数学模型相结合来观察细胞大小的不对称生长和异质性,分裂时间和伸长速度。我们发现,与耻垢分枝杆菌相反,Mtb 不仅从旧极开始细胞生长,还从新极或两极开始细胞生长。虽然大多数生物体在单细胞水平上呈指数增长,但 Mtb 具有线性生长模式。我们的数据表明,Mtb 的生长行为与模式细菌的生长行为不同,提供了 Mtb 如何生长和产生异质性的细节,并表明生长调节也可能与其他细菌不同。

更新日期:2024-11-15
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