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Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice
The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterog...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846590/ https://www.ncbi.nlm.nih.gov/pubmed/35112666 http://dx.doi.org/10.7554/eLife.74419 |
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author | Smith, Clare M Baker, Richard E Proulx, Megan K Mishra, Bibhuti B Long, Jarukit E Park, Sae Woong Lee, Ha-Na Kiritsy, Michael C Bellerose, Michelle M Olive, Andrew J Murphy, Kenan C Papavinasasundaram, Kadamba Boehm, Frederick J Reames, Charlotte J Meade, Rachel K Hampton, Brea K Linnertz, Colton L Shaw, Ginger D Hock, Pablo Bell, Timothy A Ehrt, Sabine Schnappinger, Dirk Pardo-Manuel de Villena, Fernando Ferris, Martin T Ioerger, Thomas R Sassetti, Christopher M |
author_facet | Smith, Clare M Baker, Richard E Proulx, Megan K Mishra, Bibhuti B Long, Jarukit E Park, Sae Woong Lee, Ha-Na Kiritsy, Michael C Bellerose, Michelle M Olive, Andrew J Murphy, Kenan C Papavinasasundaram, Kadamba Boehm, Frederick J Reames, Charlotte J Meade, Rachel K Hampton, Brea K Linnertz, Colton L Shaw, Ginger D Hock, Pablo Bell, Timothy A Ehrt, Sabine Schnappinger, Dirk Pardo-Manuel de Villena, Fernando Ferris, Martin T Ioerger, Thomas R Sassetti, Christopher M |
author_sort | Smith, Clare M |
collection | PubMed |
description | The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to create a resource for associating bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis of Mtb transposon mutant fitness (TnSeq) across the CC panel revealed that many virulence pathways are only required in specific host microenvironments, identifying a large fraction of the pathogen’s genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits can be associated with genetic variants distributed across the mouse genome, making the CC a unique population for identifying specific host-pathogen genetic interactions that influence pathogenesis. |
format | Online Article Text |
id | pubmed-8846590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-88465902022-02-16 Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice Smith, Clare M Baker, Richard E Proulx, Megan K Mishra, Bibhuti B Long, Jarukit E Park, Sae Woong Lee, Ha-Na Kiritsy, Michael C Bellerose, Michelle M Olive, Andrew J Murphy, Kenan C Papavinasasundaram, Kadamba Boehm, Frederick J Reames, Charlotte J Meade, Rachel K Hampton, Brea K Linnertz, Colton L Shaw, Ginger D Hock, Pablo Bell, Timothy A Ehrt, Sabine Schnappinger, Dirk Pardo-Manuel de Villena, Fernando Ferris, Martin T Ioerger, Thomas R Sassetti, Christopher M eLife Genetics and Genomics The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to create a resource for associating bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis of Mtb transposon mutant fitness (TnSeq) across the CC panel revealed that many virulence pathways are only required in specific host microenvironments, identifying a large fraction of the pathogen’s genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits can be associated with genetic variants distributed across the mouse genome, making the CC a unique population for identifying specific host-pathogen genetic interactions that influence pathogenesis. eLife Sciences Publications, Ltd 2022-02-03 /pmc/articles/PMC8846590/ /pubmed/35112666 http://dx.doi.org/10.7554/eLife.74419 Text en © 2022, Smith et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Genetics and Genomics Smith, Clare M Baker, Richard E Proulx, Megan K Mishra, Bibhuti B Long, Jarukit E Park, Sae Woong Lee, Ha-Na Kiritsy, Michael C Bellerose, Michelle M Olive, Andrew J Murphy, Kenan C Papavinasasundaram, Kadamba Boehm, Frederick J Reames, Charlotte J Meade, Rachel K Hampton, Brea K Linnertz, Colton L Shaw, Ginger D Hock, Pablo Bell, Timothy A Ehrt, Sabine Schnappinger, Dirk Pardo-Manuel de Villena, Fernando Ferris, Martin T Ioerger, Thomas R Sassetti, Christopher M Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
title | Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
title_full | Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
title_fullStr | Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
title_full_unstemmed | Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
title_short | Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
title_sort | host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846590/ https://www.ncbi.nlm.nih.gov/pubmed/35112666 http://dx.doi.org/10.7554/eLife.74419 |
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