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 in | PLoS computational biology Vol. 11; no. 4; p. e1004203 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
01.04.2015
Public Library of Science (PLoS) |
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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. |
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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 |
AuthorAffiliation_xml | – name: 2 Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America – name: 3 Center for Systems Biology, Duke University, Durham, North Carolina, United States of America – name: 1 Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America – name: University of Freiburg, GERMANY |
Author_xml | – sequence: 1 givenname: Tae J surname: Lee fullname: Lee, Tae J organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America; Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America – sequence: 2 givenname: Jeffrey surname: Wong fullname: Wong, Jeffrey organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America; Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America – sequence: 3 givenname: Sena surname: Bae fullname: Bae, Sena organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America; Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America – sequence: 4 givenname: Anna Jisu surname: Lee fullname: Lee, Anna Jisu organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America – sequence: 5 givenname: Allison surname: Lopatkin fullname: Lopatkin, Allison organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America – sequence: 6 givenname: Fan surname: Yuan fullname: Yuan, Fan organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America – sequence: 7 givenname: Lingchong surname: You fullname: You, Lingchong organization: Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America; Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America; 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 |
Copyright_xml | – notice: COPYRIGHT 2015 Public Library of Science – notice: 2015 Lee et al 2015 Lee et al – 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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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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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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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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 |
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