Kim Jinsu, Sütterlin Christine, Tan Ming, Enciso German
Department of Mathematics, Pohang University of Science Technology, Pohang, Republic of Korea.
Department of Developmental and Cell Biology, University of California, Irvine, California, United States of America.
PLoS Comput Biol. 2025 Jul 14;21(7):e1013227. doi: 10.1371/journal.pcbi.1013227. eCollection 2025 Jul.
Chlamydia is an intracellular bacterium that reproduces via an unusual developmental cycle that only occurs within a eukaryotic host cell. A replicating form of the bacterium (RB) repeatedly divides to produce about a thousand progeny, which convert in a delayed and asynchronous manner into the infectious form (EB). The regulatory mechanisms that control this developmental switch are unknown, but they could potentially include extrinsic signals from the host cell or other chlamydiae, or an intrinsic signal such as chlamydial cell size. In this paper, we investigated the regulation of RB-to-EB conversion by developing and analyzing three mathematical models, each based on a different regulatory mechanism. To test these models, we derived statistical evidence from parameters, including number, size and location of RBs and EBs, obtained from experimental measurements and model fitting. All three models successfully reproduced the experimentally measured timing of RB-to-EB conversion and growth curves of the developmental forms in an infected cell. However, only the size control model, which postulates that RB size is an intrinsic signal that regulates the timing of RB-to-EB conversion, reproduced two additional statistical properties of the intracellular infection. These properties are a positive correlation between the number of RBs and EBs throughout the developmental cycle and the monotonic evolution of the coefficient of variation of EB number. This analysis thus provides support for the size control model.
衣原体是一种细胞内细菌，它通过一种仅在真核宿主细胞内发生的异常发育周期进行繁殖。细菌的复制形式（RB）反复分裂产生约一千个后代，这些后代以延迟和异步的方式转化为感染形式（EB）。控制这种发育转换的调节机制尚不清楚，但可能包括来自宿主细胞或其他衣原体的外在信号，或诸如衣原体细胞大小等内在信号。在本文中，我们通过开发和分析三种数学模型来研究RB向EB转化的调节，每个模型基于不同的调节机制。为了测试这些模型，我们从实验测量和模型拟合获得的参数（包括RB和EB的数量、大小和位置）中得出统计证据。所有三个模型都成功地重现了实验测量的RB向EB转化的时间以及感染细胞中发育形式的生长曲线。然而，只有大小控制模型（该模型假设RB大小是调节RB向EB转化时间的内在信号）重现了细胞内感染的另外两个统计特性。这些特性是整个发育周期中RB和EB数量之间的正相关以及EB数量变异系数的单调演变。因此，该分析为大小控制模型提供了支持。
