UNIGE document Scientific Article
previous document  unige:9454  next document
add to browser collection
Title

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

Authors
Deshusses, J. M.
Koessler, Thibaud
Bento, Manuela
Stahl-Zeng, Jianru
show hidden authors show all authors [1 - 20]
Published in BMC Genomics. 2006, vol. 7, p. 296
Abstract BACKGROUND: To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of Staphylococcus aureus 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 S. aureus proteome. RESULTS: 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. CONCLUSION: 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 in vitro. 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.
Keywords Anti-Bacterial Agents/pharmacologyBiological Markers/analysis/metabolismColony Count, MicrobialCombinatorial Chemistry Techniques/methodsDrug Resistance, Microbial/geneticsGene Expression Profiling/ methodsGlycopeptides/ pharmacologyPhylogenyProteomics/ methodsStaphylococcus aureus/ drug effects/genetics
Identifiers
PMID: 17121677
Full text
Structures
Citation
(ISO format)
SCHERL, Alexander et al. Exploring glycopeptide-resistance in Staphylococcus aureus: a combined proteomics and transcriptomics approach for the identification of resistance-related markers. In: BMC Genomics, 2006, vol. 7, p. 296. https://archive-ouverte.unige.ch/unige:9454

263 hits

726 downloads

Update

Deposited on : 2010-07-12

Export document
Format :
Citation style :