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Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross
Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated diseas...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067680/ https://www.ncbi.nlm.nih.gov/pubmed/35417454 http://dx.doi.org/10.1371/journal.pgen.1010075 |
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author | Scoggin, Kristin Lynch, Rachel Gupta, Jyotsana Nagarajan, Aravindh Sheffield, Maxwell Elsaadi, Ahmed Bowden, Christopher Aminian, Manuchehr Peterson, Amy Adams, L. Garry Kirby, Michael Threadgill, David W. Andrews-Polymenis, Helene L. |
author_facet | Scoggin, Kristin Lynch, Rachel Gupta, Jyotsana Nagarajan, Aravindh Sheffield, Maxwell Elsaadi, Ahmed Bowden, Christopher Aminian, Manuchehr Peterson, Amy Adams, L. Garry Kirby, Michael Threadgill, David W. Andrews-Polymenis, Helene L. |
author_sort | Scoggin, Kristin |
collection | PubMed |
description | Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1, known to reduce survival in mice after STm infections, are located in the Chr 1 interval, and the Chr 7 association overlaps with a previously identified QTL peak called Ses2. We identified two new genetic regions on Chr 2 and 4 associated with susceptibility to STm infection. Our data reveal the diversity of responses to STm infection across a range of host genetics and identified new candidate regions for survival of STm infection. |
format | Online Article Text |
id | pubmed-9067680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-90676802022-05-05 Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross Scoggin, Kristin Lynch, Rachel Gupta, Jyotsana Nagarajan, Aravindh Sheffield, Maxwell Elsaadi, Ahmed Bowden, Christopher Aminian, Manuchehr Peterson, Amy Adams, L. Garry Kirby, Michael Threadgill, David W. Andrews-Polymenis, Helene L. PLoS Genet Research Article Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1, known to reduce survival in mice after STm infections, are located in the Chr 1 interval, and the Chr 7 association overlaps with a previously identified QTL peak called Ses2. We identified two new genetic regions on Chr 2 and 4 associated with susceptibility to STm infection. Our data reveal the diversity of responses to STm infection across a range of host genetics and identified new candidate regions for survival of STm infection. Public Library of Science 2022-04-13 /pmc/articles/PMC9067680/ /pubmed/35417454 http://dx.doi.org/10.1371/journal.pgen.1010075 Text en © 2022 Scoggin et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Scoggin, Kristin Lynch, Rachel Gupta, Jyotsana Nagarajan, Aravindh Sheffield, Maxwell Elsaadi, Ahmed Bowden, Christopher Aminian, Manuchehr Peterson, Amy Adams, L. Garry Kirby, Michael Threadgill, David W. Andrews-Polymenis, Helene L. Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross |
title | Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross |
title_full | Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross |
title_fullStr | Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross |
title_full_unstemmed | Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross |
title_short | Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross |
title_sort | genetic background influences survival of infections with salmonella enterica serovar typhimurium in the collaborative cross |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067680/ https://www.ncbi.nlm.nih.gov/pubmed/35417454 http://dx.doi.org/10.1371/journal.pgen.1010075 |
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