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Quantitative dose-response analysis untangles host bottlenecks to enteric infection
Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the diarrhea causing bacterium Citrobacter rodentium during colonization of its natural host, mice, we determine the number of cells that fo...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884216/ https://www.ncbi.nlm.nih.gov/pubmed/36709326 http://dx.doi.org/10.1038/s41467-023-36162-3 |
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author | Campbell, Ian W. Hullahalli, Karthik Turner, Jerrold R. Waldor, Matthew K. |
author_facet | Campbell, Ian W. Hullahalli, Karthik Turner, Jerrold R. Waldor, Matthew K. |
author_sort | Campbell, Ian W. |
collection | PubMed |
description | Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the diarrhea causing bacterium Citrobacter rodentium during colonization of its natural host, mice, we determine the number of cells that found the infection by establishing a replicative niche. In female mice the size of the pathogen’s founding population scales with dose and is controlled by a severe yet slow-acting bottleneck. Reducing stomach acid or changing host genotype modestly relaxes the bottleneck without breaking the fractional relationship between dose and founders. In contrast, disrupting the microbiota causes the founding population to no longer scale with the size of the inoculum and allows the pathogen to infect at almost any dose, indicating that the microbiota creates the dominant bottleneck. Further, in the absence of competition with the microbiota, the diversity of the pathogen population slowly contracts as the population is overtaken by bacteria having lost the critical virulence island, the locus of enterocyte effacement (LEE). Collectively, our findings reveal that the mechanisms of protection by colonization bottlenecks are reflected in and can be generally defined by the impact of dose on the pathogen’s founding population. |
format | Online Article Text |
id | pubmed-9884216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98842162023-01-30 Quantitative dose-response analysis untangles host bottlenecks to enteric infection Campbell, Ian W. Hullahalli, Karthik Turner, Jerrold R. Waldor, Matthew K. Nat Commun Article Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the diarrhea causing bacterium Citrobacter rodentium during colonization of its natural host, mice, we determine the number of cells that found the infection by establishing a replicative niche. In female mice the size of the pathogen’s founding population scales with dose and is controlled by a severe yet slow-acting bottleneck. Reducing stomach acid or changing host genotype modestly relaxes the bottleneck without breaking the fractional relationship between dose and founders. In contrast, disrupting the microbiota causes the founding population to no longer scale with the size of the inoculum and allows the pathogen to infect at almost any dose, indicating that the microbiota creates the dominant bottleneck. Further, in the absence of competition with the microbiota, the diversity of the pathogen population slowly contracts as the population is overtaken by bacteria having lost the critical virulence island, the locus of enterocyte effacement (LEE). Collectively, our findings reveal that the mechanisms of protection by colonization bottlenecks are reflected in and can be generally defined by the impact of dose on the pathogen’s founding population. Nature Publishing Group UK 2023-01-28 /pmc/articles/PMC9884216/ /pubmed/36709326 http://dx.doi.org/10.1038/s41467-023-36162-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Campbell, Ian W. Hullahalli, Karthik Turner, Jerrold R. Waldor, Matthew K. Quantitative dose-response analysis untangles host bottlenecks to enteric infection |
title | Quantitative dose-response analysis untangles host bottlenecks to enteric infection |
title_full | Quantitative dose-response analysis untangles host bottlenecks to enteric infection |
title_fullStr | Quantitative dose-response analysis untangles host bottlenecks to enteric infection |
title_full_unstemmed | Quantitative dose-response analysis untangles host bottlenecks to enteric infection |
title_short | Quantitative dose-response analysis untangles host bottlenecks to enteric infection |
title_sort | quantitative dose-response analysis untangles host bottlenecks to enteric infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884216/ https://www.ncbi.nlm.nih.gov/pubmed/36709326 http://dx.doi.org/10.1038/s41467-023-36162-3 |
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