Cargando…
A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep
BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to impr...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706528/ https://www.ncbi.nlm.nih.gov/pubmed/23874438 http://dx.doi.org/10.1371/journal.pone.0067677 |
_version_ | 1782476569038553088 |
---|---|
author | Collie, David Govan, John Wright, Steven Thornton, Elisabeth Tennant, Peter Smith, Sionagh Doherty, Catherine McLachlan, Gerry |
author_facet | Collie, David Govan, John Wright, Steven Thornton, Elisabeth Tennant, Peter Smith, Sionagh Doherty, Catherine McLachlan, Gerry |
author_sort | Collie, David |
collection | PubMed |
description | BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. METHODOLOGY/PRINCIPAL FINDINGS: Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g). CONCLUSIONS/SIGNIFICANCE: The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches. |
format | Online Article Text |
id | pubmed-3706528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37065282013-07-19 A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep Collie, David Govan, John Wright, Steven Thornton, Elisabeth Tennant, Peter Smith, Sionagh Doherty, Catherine McLachlan, Gerry PLoS One Research Article BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. METHODOLOGY/PRINCIPAL FINDINGS: Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g). CONCLUSIONS/SIGNIFICANCE: The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches. Public Library of Science 2013-07-09 /pmc/articles/PMC3706528/ /pubmed/23874438 http://dx.doi.org/10.1371/journal.pone.0067677 Text en © 2013 Collie et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Collie, David Govan, John Wright, Steven Thornton, Elisabeth Tennant, Peter Smith, Sionagh Doherty, Catherine McLachlan, Gerry A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep |
title | A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep |
title_full | A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep |
title_fullStr | A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep |
title_full_unstemmed | A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep |
title_short | A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep |
title_sort | lung segmental model of chronic pseudomonas infection in sheep |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706528/ https://www.ncbi.nlm.nih.gov/pubmed/23874438 http://dx.doi.org/10.1371/journal.pone.0067677 |
work_keys_str_mv | AT colliedavid alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT govanjohn alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT wrightsteven alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT thorntonelisabeth alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT tennantpeter alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT smithsionagh alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT dohertycatherine alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT mclachlangerry alungsegmentalmodelofchronicpseudomonasinfectioninsheep AT colliedavid lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT govanjohn lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT wrightsteven lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT thorntonelisabeth lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT tennantpeter lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT smithsionagh lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT dohertycatherine lungsegmentalmodelofchronicpseudomonasinfectioninsheep AT mclachlangerry lungsegmentalmodelofchronicpseudomonasinfectioninsheep |