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Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model

Linezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is a cell wall active agent. Here, we used a murine sepsis model to test the hypothesis that L treatment is associated with differences in bact...

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Autores principales: Sharma-Kuinkel, Batu K., Zhang, Yurong, Yan, Qin, Ahn, Sun Hee, Fowler, Vance G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614971/
https://www.ncbi.nlm.nih.gov/pubmed/23565251
http://dx.doi.org/10.1371/journal.pone.0060463
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author Sharma-Kuinkel, Batu K.
Zhang, Yurong
Yan, Qin
Ahn, Sun Hee
Fowler, Vance G.
author_facet Sharma-Kuinkel, Batu K.
Zhang, Yurong
Yan, Qin
Ahn, Sun Hee
Fowler, Vance G.
author_sort Sharma-Kuinkel, Batu K.
collection PubMed
description Linezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is a cell wall active agent. Here, we used a murine sepsis model to test the hypothesis that L treatment is associated with differences in bacterial and host characteristics as compared to V. Mice were injected with S. aureus USA300, and then intravenously treated with 25 mg/kg of either L or V at 2 hours post infection (hpi). In vivo alpha-hemolysin production was reduced in both L and V-treated mice compared to untreated mice but the reduction did not reach the statistical significance [P = 0.12 for L; P = 0.70 for V). PVL was significantly reduced in L-treated mice compared to untreated mice (P = 0.02). However the reduction of in vivo PVL did not reach the statistical significance in V- treated mice compared to untreated mice (P = 0.27). Both antibiotics significantly reduced IL-1β production [P = 0.001 for L; P = 0.006 for V]. IL-6 was significantly reduced with L but not V antibiotic treatment [P<0.001 for L; P = 0.11 for V]. Neither treatment significantly reduced production of TNF-α. Whole-blood gene expression profiling showed no significant effect of L and V on uninfected mice. In S. aureus-infected mice, L altered the expression of a greater number of genes than V (95 vs. 42; P = 0.001). Pathway analysis for the differentially expressed genes identified toll-like receptor signaling pathway to be common to each S. aureus-infected comparison. Expression of immunomodulatory genes like Cxcl9, Cxcl10, Il1r2, Cd14 and Nfkbia was different among the treatment groups. Glycerolipid metabolism pathway was uniquely associated with L treatment in S. aureus infection. This study demonstrates that, as compared to V, treatment with L is associated with reduced levels of toxin production, differences in host inflammatory response, and distinct host gene expression characteristics in MRSA sepsis.
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spelling pubmed-36149712013-04-05 Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model Sharma-Kuinkel, Batu K. Zhang, Yurong Yan, Qin Ahn, Sun Hee Fowler, Vance G. PLoS One Research Article Linezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is a cell wall active agent. Here, we used a murine sepsis model to test the hypothesis that L treatment is associated with differences in bacterial and host characteristics as compared to V. Mice were injected with S. aureus USA300, and then intravenously treated with 25 mg/kg of either L or V at 2 hours post infection (hpi). In vivo alpha-hemolysin production was reduced in both L and V-treated mice compared to untreated mice but the reduction did not reach the statistical significance [P = 0.12 for L; P = 0.70 for V). PVL was significantly reduced in L-treated mice compared to untreated mice (P = 0.02). However the reduction of in vivo PVL did not reach the statistical significance in V- treated mice compared to untreated mice (P = 0.27). Both antibiotics significantly reduced IL-1β production [P = 0.001 for L; P = 0.006 for V]. IL-6 was significantly reduced with L but not V antibiotic treatment [P<0.001 for L; P = 0.11 for V]. Neither treatment significantly reduced production of TNF-α. Whole-blood gene expression profiling showed no significant effect of L and V on uninfected mice. In S. aureus-infected mice, L altered the expression of a greater number of genes than V (95 vs. 42; P = 0.001). Pathway analysis for the differentially expressed genes identified toll-like receptor signaling pathway to be common to each S. aureus-infected comparison. Expression of immunomodulatory genes like Cxcl9, Cxcl10, Il1r2, Cd14 and Nfkbia was different among the treatment groups. Glycerolipid metabolism pathway was uniquely associated with L treatment in S. aureus infection. This study demonstrates that, as compared to V, treatment with L is associated with reduced levels of toxin production, differences in host inflammatory response, and distinct host gene expression characteristics in MRSA sepsis. Public Library of Science 2013-04-02 /pmc/articles/PMC3614971/ /pubmed/23565251 http://dx.doi.org/10.1371/journal.pone.0060463 Text en © 2013 Sharma-Kuinkel 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
Sharma-Kuinkel, Batu K.
Zhang, Yurong
Yan, Qin
Ahn, Sun Hee
Fowler, Vance G.
Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model
title Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model
title_full Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model
title_fullStr Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model
title_full_unstemmed Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model
title_short Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model
title_sort host gene expression profiling and in vivo cytokine studies to characterize the role of linezolid and vancomycin in methicillin-resistant staphylococcus aureus (mrsa) murine sepsis model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614971/
https://www.ncbi.nlm.nih.gov/pubmed/23565251
http://dx.doi.org/10.1371/journal.pone.0060463
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