A power-law dependence of bacterial invasion on mammalian host receptors

Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical ce...

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Published inPLoS computational biology Vol. 11; no. 4; p. e1004203
Main Authors Lee, Tae J, Wong, Jeffrey, Bae, Sena, Lee, Anna Jisu, Lopatkin, Allison, Yuan, Fan, You, Lingchong
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.04.2015
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Abstract Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host β1-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.
AbstractList Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host [[beta].sub.1]-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.
Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia , which enables uptake via mammalian host β 1 -integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines. Uptake of bacteria by mammalian cells is highly variable within a population of host cells and between host cell types. A detailed but unwieldy mechanistic model describing individual host-pathogen receptor binding events is captured by a simple power-law dependence on the concentration of the host receptors. The power-law parameters capture characteristics of the host-bacterium pair interaction and can differentiate host cell lines. This study has important implications for understanding the accuracy and precision of therapeutics employing receptor-mediated transport of materials to mammalian hosts.
Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host β1-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.
  Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host β1-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.
Audience Academic
Author You, Lingchong
Bae, Sena
Lee, Anna Jisu
Yuan, Fan
Lopatkin, Allison
Lee, Tae J
Wong, Jeffrey
AuthorAffiliation 2 Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America
University of Freiburg, GERMANY
1 Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America
3 Center for Systems Biology, Duke University, Durham, North Carolina, United States of America
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Copyright COPYRIGHT 2015 Public Library of Science
2015 Lee et al 2015 Lee et al
2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Lee TJ, Wong J, Bae S, Lee AJ, Lopatkin A, Yuan F, et al. (2015) A Power-Law Dependence of Bacterial Invasion on Mammalian Host Receptors. PLoS Comput Biol 11(4): e1004203. doi:10.1371/journal.pcbi.1004203
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– notice: 2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Lee TJ, Wong J, Bae S, Lee AJ, Lopatkin A, Yuan F, et al. (2015) A Power-Law Dependence of Bacterial Invasion on Mammalian Host Receptors. PLoS Comput Biol 11(4): e1004203. doi:10.1371/journal.pcbi.1004203
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Conceived and designed the experiments: TJL LY JW SB. Performed the experiments: TJL SB. Analyzed the data: TJL JW SB AJL LY. Contributed reagents/materials/analysis tools: LY FY. Wrote the paper: TJL JW SB AJL AL FY LY. Implemented and analyzed the kinetic models: TJL JW.
Current address: Orthopedic Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
The authors have declared that no competing interests exist.
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SSID ssj0035896
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Snippet Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake...
Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake...
  Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake...
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SourceType Open Website
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StartPage e1004203
SubjectTerms Bacteria
Bacteria - metabolism
Bacteria - pathogenicity
Bacterial Adhesion
Bacterial Infections
Bacterial Proteins - metabolism
Computational Biology
Dependence
E coli
Escherichia coli
Experiments
Flow cytometry
Health aspects
HeLa Cells
Host-bacteria relationships
Host-Pathogen Interactions - physiology
Humans
Identification and classification
Listeria
Mathematical models
Membrane Proteins - metabolism
Models, Biological
Ordinary differential equations
Yersinia
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Title A power-law dependence of bacterial invasion on mammalian host receptors
URI https://www.ncbi.nlm.nih.gov/pubmed/25879937
https://search.proquest.com/docview/1674203616
https://pubmed.ncbi.nlm.nih.gov/PMC4399907
https://doaj.org/article/abf2c99069564870a09db80ca4050316
http://dx.doi.org/10.1371/journal.pcbi.1004203
Volume 11
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