Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
复制标题
在抗生素处理过程中，映射对种群级动力学的单细胞响应
DOI：
10.15252/msb.202211475
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发表时间：
2023-05-10
影响因子：
9.9
通讯作者：
You, Lingchong
中科院分区：
文献类型：
--
作者：
Kim, Kyeri;Wang, Teng;Ma, Helena R.;Simsek, Emrah;Li, Boyan;Andreani, Virgile;You, Lingchong
关键词：
用β-内酰胺类抗生素治疗敏感细菌通常会导致两个显著的群体水平特征：总群体生物量在随后下降之前短暂增加，以及生长和杀灭率之间的线性相关性。然而，目前尚不清楚这些群体水平的反应如何从集体单细胞反应中产生。在β-内酰胺处理过程中，众所周知，单个细胞在裂解前通常表现出不同程度的裂解。我们发现，细胞裂解的累积概率随着细胞裂解的程度呈S形增加，这种依赖性的特征在于细菌菌株，抗生素剂量和生长条件的独特参数。建模证明了单细胞裂解概率如何引起种群水平的生物量动力学，这是经过实验验证的。该映射提供了对群体生物量时间杀灭曲线如何从单细胞中出现的见解，并允许用通用参数表示单细胞和群体水平的响应。抗生素治疗后，群体水平的反应如何从集体单细胞反应中产生？在用β-内酰胺处理的单细胞中测量细菌伸长和裂解的动力学允许定量映射到时间群体生物量动力学。
Treatment of sensitive bacteria with beta‐lactam antibiotics often leads to two salient population‐level features: a transient increase in total population biomass before a subsequent decline, and a linear correlation between growth and killing rates. However, it remains unclear how these population‐level responses emerge from collective single‐cell responses. During beta‐lactam treatment, it is well‐recognized that individual cells often exhibit varying degrees of filamentation before lysis. We show that the cumulative probability of cell lysis increases sigmoidally with the extent of filamentation and that this dependence is characterized by unique parameters that are specific to bacterial strain, antibiotic dose, and growth condition. Modeling demonstrates how the single‐cell lysis probabilities can give rise to population‐level biomass dynamics, which were experimentally validated. This mapping provides insights into how the population biomass time‐kill curve emerges from single cells and allows the representation of both single‐ and population‐level responses with universal parameters. How do population‐level responses emerge from collective single‐cell responses upon antibiotic treatment? Measuring the kinetics of bacterial elongation and lysis in single cells treated with beta‐lactams allows quantitative mapping to temporal population biomass dynamics.
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DOI：
10.1073/pnas.0805309105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Huang, Kerwyn Casey;Mukhopadhyay, Ranjan;Wingreen, Ned S.
通讯作者：
Wingreen, Ned S.
影响因子：
4.9
作者：
ENG, RHK;CHERUBIN, C;BUCCINI, F
通讯作者：
BUCCINI, F
影响因子：
2.4
作者：
Daly, Kristopher E.;Huang, Kerwyn Casey;Mukhopadhyay, Ranjan
通讯作者：
Mukhopadhyay, Ranjan
影响因子：
4.2
作者：
Kjeldsen, Thea S. B.;Sommer, Morten O. A.;Olsen, John E.
通讯作者：
Olsen, John E.
影响因子：
14.2
作者：
Buijs, J.;Dofferhoff, A. S. M.;van der Meer, J. W. M.
通讯作者：
van der Meer, J. W. M.