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Gene expression analysis of Daptomycin resistance in Stapyloccoccus aureus strains: 2818 and 2819.

ABSTRACT: The study aims to identify genes associated with daptomycin resistance.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE26249 | GEO | 2011/04/08

SECONDARY ACCESSION(S): PRJNA135079

REPOSITORIES: GEO

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Project description:Objectives: Development of daptomycin resistance (DAPR) in Staphylococcus aureus is associated with clinical treatment failures. Mechanism(s) of such resistance has not been clearly defined. Methods: We studied an isogenic daptomycin-susceptible (DAPS) and daptomycin-resistant (DAPR) S. aureus strain pair (616; 701) from a patient with relapsing endocarditis during daptomycin treatment, using comparative transcriptomic and proteomic techniques. Results. Minor differences in genome content were found between strains by DNA hybridization. Transcriptomic analyses identified a number of genes differentially expressed in important functional categories: cell division, metabolism of bacterial envelopes and global regulation. Of note, the DAPR isolate exhibited reduced expression of the major cell wall autolysis gene coincident with upregulation of genes involved in wall teichoic acid production. Using quantitative (q)RT-PCR on gene cadre putatively involved in cationic peptide resistance, we formulated a putative regulatory network compatible with microarray data-sets, mainly implicating bacterial envelopes. Of interest, qRT-PCR of this same gene cadre from two distinct isogenic DAPS/DAPR clinical strain pairs revealed evidence of other strain dependent networks operative in the DAPR phenotype. Comparative proteomics of 616 vs 701 revealed differential abundance of proteins in various functional categories including: cell-wall associated targets and biofilm-formation proteins. Phenotypically, strains 616 and 701 showed major differences in ability to develop bacterial biofilms in presence of the antibacterial lipid, oleic acid. Conclusions: Compatible with previous in vitro observations, in vivo acquired DAPR in S. aureus is a complex, multistep phenomenon allowing for: i) strain dependent phenotypes; ii) transcriptome adaptation; and iii) modification of lipid and protein content of cellular envelopes. Daptomycin suceptible strain vs daptomycin non suceptible strain after daptomycin treatment

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Gene expression analysis of Daptomycin resistance in Stapyloccoccus aureus strains: 2818 and 2819.

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