Mapping single‐cell responses to population‐level dynamics during antibiotic treatment

Abstract 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 p...

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Main Authors: Kyeri Kim, Teng Wang, Helena R Ma, Emrah Şimşek, Boyan Li, Virgile Andreani, Lingchong You
Format: Article
Language:English
Published: Springer Nature 2023-05-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.15252/msb.202211475
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author Kyeri Kim
Teng Wang
Helena R Ma
Emrah Şimşek
Boyan Li
Virgile Andreani
Lingchong You
author_facet Kyeri Kim
Teng Wang
Helena R Ma
Emrah Şimşek
Boyan Li
Virgile Andreani
Lingchong You
author_sort Kyeri Kim
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 1744-4292
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publishDate 2023-05-01
publisher Springer Nature
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series Molecular Systems Biology
spelling doaj-art-5d06eea2d468425f9e0c7629c2a905932025-08-20T03:43:31ZengSpringer NatureMolecular Systems Biology1744-42922023-05-0119711310.15252/msb.202211475Mapping single‐cell responses to population‐level dynamics during antibiotic treatmentKyeri Kim0Teng Wang1Helena R Ma2Emrah Şimşek3Boyan Li4Virgile Andreani5Lingchong You6Department of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityIntegrated Science Program, Yuanpei College, Peking UniversityBiomedical Engineering Department, Boston UniversityDepartment of Biomedical Engineering, Duke UniversityAbstract 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.https://doi.org/10.15252/msb.202211475antibiotic responsebacterial population dynamicsfilamentationquantitative biologysingle‐cell analysis
spellingShingle Kyeri Kim
Teng Wang
Helena R Ma
Emrah Şimşek
Boyan Li
Virgile Andreani
Lingchong You
Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
Molecular Systems Biology
antibiotic response
bacterial population dynamics
filamentation
quantitative biology
single‐cell analysis
title Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
title_full Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
title_fullStr Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
title_full_unstemmed Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
title_short Mapping single‐cell responses to population‐level dynamics during antibiotic treatment
title_sort mapping single cell responses to population level dynamics during antibiotic treatment
topic antibiotic response
bacterial population dynamics
filamentation
quantitative biology
single‐cell analysis
url https://doi.org/10.15252/msb.202211475
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AT emrahsimsek mappingsinglecellresponsestopopulationleveldynamicsduringantibiotictreatment
AT boyanli mappingsinglecellresponsestopopulationleveldynamicsduringantibiotictreatment
AT virgileandreani mappingsinglecellresponsestopopulationleveldynamicsduringantibiotictreatment
AT lingchongyou mappingsinglecellresponsestopopulationleveldynamicsduringantibiotictreatment