Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers

<p>Abstract</p> <p>Background</p> <p>To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of <it>Staphylococcus aureus </it>with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome m...

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Main Authors: Renzoni Adriana, Gallé Francesca, Vaezzadeh Alireza, Masselot Alexandre, Fischer Adrien, Stahl-Zeng Jianru, Bento Manuela, Huyghe Antoine, Koessler Thibaud, Deshusses Jacques M, Charbonnier Yvan, François Patrice, Scherl Alexander, Vaudaux Pierre, Lew Daniel, Zimmermann-Ivol Catherine G, Binz Pierre-Alain, Sanchez Jean-Charles, Hochstrasser Denis F, Schrenzel Jacques
Format: Article
Language:English
Published: BMC 2006-11-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/7/296
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spelling doaj-0260980a67d84251b8123c9e9d8beba02020-11-25T01:57:22ZengBMCBMC Genomics1471-21642006-11-017129610.1186/1471-2164-7-296Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markersRenzoni AdrianaGallé FrancescaVaezzadeh AlirezaMasselot AlexandreFischer AdrienStahl-Zeng JianruBento ManuelaHuyghe AntoineKoessler ThibaudDeshusses Jacques MCharbonnier YvanFrançois PatriceScherl AlexanderVaudaux PierreLew DanielZimmermann-Ivol Catherine GBinz Pierre-AlainSanchez Jean-CharlesHochstrasser Denis FSchrenzel Jacques<p>Abstract</p> <p>Background</p> <p>To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of <it>Staphylococcus aureus </it>with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome microarray-based transcription and quantitative proteomic profiling. Quantitative proteomics performed on membrane extracts showed exquisite inter-experimental reproducibility permitting the identification and relative quantification of >30% of the predicted <it>S. aureus </it>proteome.</p> <p>Results</p> <p>In the absence of antibiotic selection pressure, comparison of stable resistant and susceptible strains revealed 94 differentially expressed genes and 178 proteins. As expected, only partial correlation was obtained between transcriptomic and proteomic results during stationary-phase. Application of massively parallel methods identified one third of the complete proteome, a majority of which was only predicted based on genome sequencing, but never identified to date. Several over-expressed genes represent previously reported targets, while series of genes and proteins possibly involved in the glycopeptide resistance mechanism were discovered here, including regulators, global regulator attenuator, hyper-mutability factor or hypothetical proteins. Gene expression of these markers was confirmed in a collection of genetically unrelated strains showing altered susceptibility to glycopeptides.</p> <p>Conclusion</p> <p>Our proteome and transcriptome analyses have been performed during stationary-phase of growth on isogenic strains showing susceptibility or intermediate level of resistance against glycopeptides. Altered susceptibility had emerged spontaneously after infection with a sensitive parental strain, thus not selected <it>in vitro</it>. This combined analysis allows the identification of hundreds of proteins considered, so far as hypothetical protein. In addition, this study provides not only a global picture of transcription and expression adaptations during a complex antibiotic resistance mechanism but also unravels potential drug targets or markers that are constitutively expressed by resistant strains regardless of their genetic background, amenable to be used as diagnostic targets.</p> http://www.biomedcentral.com/1471-2164/7/296
collection DOAJ
language English
format Article
sources DOAJ
author Renzoni Adriana
Gallé Francesca
Vaezzadeh Alireza
Masselot Alexandre
Fischer Adrien
Stahl-Zeng Jianru
Bento Manuela
Huyghe Antoine
Koessler Thibaud
Deshusses Jacques M
Charbonnier Yvan
François Patrice
Scherl Alexander
Vaudaux Pierre
Lew Daniel
Zimmermann-Ivol Catherine G
Binz Pierre-Alain
Sanchez Jean-Charles
Hochstrasser Denis F
Schrenzel Jacques
spellingShingle Renzoni Adriana
Gallé Francesca
Vaezzadeh Alireza
Masselot Alexandre
Fischer Adrien
Stahl-Zeng Jianru
Bento Manuela
Huyghe Antoine
Koessler Thibaud
Deshusses Jacques M
Charbonnier Yvan
François Patrice
Scherl Alexander
Vaudaux Pierre
Lew Daniel
Zimmermann-Ivol Catherine G
Binz Pierre-Alain
Sanchez Jean-Charles
Hochstrasser Denis F
Schrenzel Jacques
Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
BMC Genomics
author_facet Renzoni Adriana
Gallé Francesca
Vaezzadeh Alireza
Masselot Alexandre
Fischer Adrien
Stahl-Zeng Jianru
Bento Manuela
Huyghe Antoine
Koessler Thibaud
Deshusses Jacques M
Charbonnier Yvan
François Patrice
Scherl Alexander
Vaudaux Pierre
Lew Daniel
Zimmermann-Ivol Catherine G
Binz Pierre-Alain
Sanchez Jean-Charles
Hochstrasser Denis F
Schrenzel Jacques
author_sort Renzoni Adriana
title Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
title_short Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
title_full Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
title_fullStr Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
title_full_unstemmed Exploring glycopeptide-resistance in <it>Staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
title_sort exploring glycopeptide-resistance in <it>staphylococcus aureus</it>: a combined proteomics and transcriptomics approach for the identification of resistance-related markers
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2006-11-01
description <p>Abstract</p> <p>Background</p> <p>To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of <it>Staphylococcus aureus </it>with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome microarray-based transcription and quantitative proteomic profiling. Quantitative proteomics performed on membrane extracts showed exquisite inter-experimental reproducibility permitting the identification and relative quantification of >30% of the predicted <it>S. aureus </it>proteome.</p> <p>Results</p> <p>In the absence of antibiotic selection pressure, comparison of stable resistant and susceptible strains revealed 94 differentially expressed genes and 178 proteins. As expected, only partial correlation was obtained between transcriptomic and proteomic results during stationary-phase. Application of massively parallel methods identified one third of the complete proteome, a majority of which was only predicted based on genome sequencing, but never identified to date. Several over-expressed genes represent previously reported targets, while series of genes and proteins possibly involved in the glycopeptide resistance mechanism were discovered here, including regulators, global regulator attenuator, hyper-mutability factor or hypothetical proteins. Gene expression of these markers was confirmed in a collection of genetically unrelated strains showing altered susceptibility to glycopeptides.</p> <p>Conclusion</p> <p>Our proteome and transcriptome analyses have been performed during stationary-phase of growth on isogenic strains showing susceptibility or intermediate level of resistance against glycopeptides. Altered susceptibility had emerged spontaneously after infection with a sensitive parental strain, thus not selected <it>in vitro</it>. This combined analysis allows the identification of hundreds of proteins considered, so far as hypothetical protein. In addition, this study provides not only a global picture of transcription and expression adaptations during a complex antibiotic resistance mechanism but also unravels potential drug targets or markers that are constitutively expressed by resistant strains regardless of their genetic background, amenable to be used as diagnostic targets.</p>
url http://www.biomedcentral.com/1471-2164/7/296
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