Chung Eun Seon, Kar Prathitha, Kamkaew Maliwan, Amir Ariel, Aldridge Bree B
bioRxiv. 2023 May 17:2023.05.17.541183. doi: 10.1101/2023.05.17.541183.
The ability of bacterial pathogens to regulate growth is crucial to control homeostasis, virulence, and drug response. Yet, we do not understand the growth and cell cycle behaviors of (Mtb), a slow-growing pathogen, at the single-cell level. Here, we use time-lapse imaging and mathematical modeling to characterize these fundamental properties of Mtb. Whereas most organisms grow exponentially at the single-cell level, we find that Mtb exhibits a unique linear growth mode. Mtb growth characteristics are highly variable from cell-to-cell, notably in their growth speeds, cell cycle timing, and cell sizes. Together, our study demonstrates that growth behavior of Mtb diverges from what we have learned from model bacteria. Instead, Mtb generates a heterogeneous population while growing slowly and linearly. Our study provides a new level of detail into how Mtb grows and creates heterogeneity, and motivates more studies of growth behaviors in bacterial pathogens.
细菌病原体调节生长的能力对于维持体内平衡、毒力和药物反应的控制至关重要。然而,我们并不了解生长缓慢的病原体结核分枝杆菌(Mtb)在单细胞水平上的生长和细胞周期行为。在此,我们使用延时成像和数学建模来表征Mtb的这些基本特性。虽然大多数生物体在单细胞水平上呈指数生长,但我们发现Mtb呈现出独特的线性生长模式。Mtb的生长特性在细胞间高度可变,尤其是在生长速度、细胞周期时间和细胞大小方面。总之,我们的研究表明,Mtb的生长行为与我们从模式细菌中学到的不同。相反,Mtb在缓慢线性生长的同时产生了一个异质群体。我们的研究为Mtb如何生长并产生异质性提供了新的详细层面,并促使人们对细菌病原体的生长行为进行更多研究。