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Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice
BACKGROUND: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866434/ https://www.ncbi.nlm.nih.gov/pubmed/27169516 http://dx.doi.org/10.1186/s12864-016-2676-4 |
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author | De Simone, Maura Spagnuolo, Lorenza Lorè, Nicola Ivan Cigana, Cristina De Fino, Ida Broman, Karl W. Iraqi, Fuad A. Bragonzi, Alessandra |
author_facet | De Simone, Maura Spagnuolo, Lorenza Lorè, Nicola Ivan Cigana, Cristina De Fino, Ida Broman, Karl W. Iraqi, Fuad A. Bragonzi, Alessandra |
author_sort | De Simone, Maura |
collection | PubMed |
description | BACKGROUND: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. RESULTS: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. CONCLUSIONS: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2676-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4866434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48664342016-05-14 Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice De Simone, Maura Spagnuolo, Lorenza Lorè, Nicola Ivan Cigana, Cristina De Fino, Ida Broman, Karl W. Iraqi, Fuad A. Bragonzi, Alessandra BMC Genomics Research Article BACKGROUND: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. RESULTS: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. CONCLUSIONS: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2676-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-11 /pmc/articles/PMC4866434/ /pubmed/27169516 http://dx.doi.org/10.1186/s12864-016-2676-4 Text en © De Simone et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article De Simone, Maura Spagnuolo, Lorenza Lorè, Nicola Ivan Cigana, Cristina De Fino, Ida Broman, Karl W. Iraqi, Fuad A. Bragonzi, Alessandra Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice |
title | Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice |
title_full | Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice |
title_fullStr | Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice |
title_full_unstemmed | Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice |
title_short | Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice |
title_sort | mapping genetic determinants of host susceptibility to pseudomonas aeruginosa lung infection in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866434/ https://www.ncbi.nlm.nih.gov/pubmed/27169516 http://dx.doi.org/10.1186/s12864-016-2676-4 |
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