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In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection
PURPOSE: To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207797/ https://www.ncbi.nlm.nih.gov/pubmed/25340474 http://dx.doi.org/10.1371/journal.pone.0110872 |
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author | Sadaka, Ama Palmer, Kelli Suzuki, Takashi Gilmore, Michael S. |
author_facet | Sadaka, Ama Palmer, Kelli Suzuki, Takashi Gilmore, Michael S. |
author_sort | Sadaka, Ama |
collection | PubMed |
description | PURPOSE: To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model. METHODS: For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored. RESULTS: Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection. CONCLUSION: Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity. |
format | Online Article Text |
id | pubmed-4207797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42077972014-10-27 In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection Sadaka, Ama Palmer, Kelli Suzuki, Takashi Gilmore, Michael S. PLoS One Research Article PURPOSE: To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model. METHODS: For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored. RESULTS: Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection. CONCLUSION: Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity. Public Library of Science 2014-10-23 /pmc/articles/PMC4207797/ /pubmed/25340474 http://dx.doi.org/10.1371/journal.pone.0110872 Text en © 2014 Sadaka 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 Sadaka, Ama Palmer, Kelli Suzuki, Takashi Gilmore, Michael S. In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection |
title |
In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection |
title_full |
In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection |
title_fullStr |
In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection |
title_full_unstemmed |
In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection |
title_short |
In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection |
title_sort | in vitro and in vivo models of staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207797/ https://www.ncbi.nlm.nih.gov/pubmed/25340474 http://dx.doi.org/10.1371/journal.pone.0110872 |
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