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Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography

BACKGROUND: S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been...

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Autores principales: Mason, William Jeffrey, Skaar, Eric Patrick
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723934/
https://www.ncbi.nlm.nih.gov/pubmed/19688098
http://dx.doi.org/10.1371/journal.pone.0006668
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author Mason, William Jeffrey
Skaar, Eric Patrick
author_facet Mason, William Jeffrey
Skaar, Eric Patrick
author_sort Mason, William Jeffrey
collection PubMed
description BACKGROUND: S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been elucidated. In addition, the use of computed tomography (CT) for the evaluation of staphylococcal pneumonia and its correlation to pathologic examination of infected lung tissue has not been performed to date. We have applied CT-based imaging to a murine model of staphylococcal pneumonia to determine the virulence contribution of heme-iron acquisition through the Hts and Isd systems. METHODOLOGY/PRINCIPAL FINDINGS: Mice were intranasally inoculated with ∼1.0×10(8) colony forming units (CFU) of S. aureus. Lungs from mice infected with wild type S. aureus or strains deficient in isdB and isdH (ΔisdBH) or htsA and isdE (ΔhtsAΔisdE) were harvested at 24 hours. Histology, radiographic appearance by computed tomography (CT), percent mortality and bacterial burden were evaluated. Infection with S. aureus ΔisdBH and ΔhtsAΔisdE did not result in a statistically significant difference in mortality or bacterial burden as compared to controls. CT imaging of infected mice also did not reveal an appreciable difference between the various strains when compared to wild type, but did correlate with pathologic findings of pneumonia. However, a systemic model of infection using the ΔhtsAΔisdE strain revealed a statistically significant decrease in bacterial burden in the lung, heart and kidneys. CONCLUSIONS/SIGNIFICANCE: The development of staphylococcal pneumonia in this murine model is not dependent on hemoglobin binding or heme-iron uptake into S. aureus. However, this model does reveal that heme-iron acquisition contributes to the pathogenesis of systemic staphylococcal infections. In addition, CT imaging of murine lungs is an attractive adjunct to histologic analysis for the confirmation and staging of pneumonia.
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spelling pubmed-27239342009-08-18 Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography Mason, William Jeffrey Skaar, Eric Patrick PLoS One Research Article BACKGROUND: S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been elucidated. In addition, the use of computed tomography (CT) for the evaluation of staphylococcal pneumonia and its correlation to pathologic examination of infected lung tissue has not been performed to date. We have applied CT-based imaging to a murine model of staphylococcal pneumonia to determine the virulence contribution of heme-iron acquisition through the Hts and Isd systems. METHODOLOGY/PRINCIPAL FINDINGS: Mice were intranasally inoculated with ∼1.0×10(8) colony forming units (CFU) of S. aureus. Lungs from mice infected with wild type S. aureus or strains deficient in isdB and isdH (ΔisdBH) or htsA and isdE (ΔhtsAΔisdE) were harvested at 24 hours. Histology, radiographic appearance by computed tomography (CT), percent mortality and bacterial burden were evaluated. Infection with S. aureus ΔisdBH and ΔhtsAΔisdE did not result in a statistically significant difference in mortality or bacterial burden as compared to controls. CT imaging of infected mice also did not reveal an appreciable difference between the various strains when compared to wild type, but did correlate with pathologic findings of pneumonia. However, a systemic model of infection using the ΔhtsAΔisdE strain revealed a statistically significant decrease in bacterial burden in the lung, heart and kidneys. CONCLUSIONS/SIGNIFICANCE: The development of staphylococcal pneumonia in this murine model is not dependent on hemoglobin binding or heme-iron uptake into S. aureus. However, this model does reveal that heme-iron acquisition contributes to the pathogenesis of systemic staphylococcal infections. In addition, CT imaging of murine lungs is an attractive adjunct to histologic analysis for the confirmation and staging of pneumonia. Public Library of Science 2009-08-18 /pmc/articles/PMC2723934/ /pubmed/19688098 http://dx.doi.org/10.1371/journal.pone.0006668 Text en Mason, Skaar. 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
Mason, William Jeffrey
Skaar, Eric Patrick
Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography
title Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography
title_full Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography
title_fullStr Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography
title_full_unstemmed Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography
title_short Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography
title_sort assessing the contribution of heme-iron acquisition to staphylococcus aureus pneumonia using computed tomography
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723934/
https://www.ncbi.nlm.nih.gov/pubmed/19688098
http://dx.doi.org/10.1371/journal.pone.0006668
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