|
| Status |
Public on Dec 02, 2011 |
| Title |
Daptomycin-Resistance Mechanisms in Clinically-Derived Staphylococcus aureus Strains Assessed by a Combined Transcriptomics and Proteomics Approach |
| Platform organisms |
Staphylococcus aureus; Staphylococcus aureus subsp. aureus NCTC 8325; Staphylococcus aureus subsp. aureus COL; Staphylococcus aureus subsp. aureus Mu50; Staphylococcus aureus subsp. aureus N315; Staphylococcus aureus subsp. aureus MW2; Staphylococcus aureus subsp. aureus MRSA252; Staphylococcus aureus subsp. aureus MSSA476; Staphylococcus aureus subsp. aureus USA300 |
| Sample organism |
Staphylococcus aureus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| Overall design |
Daptomycin suceptible strain vs daptomycin non suceptible strain after daptomycin treatment
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| Contributor(s) |
Fischer A, Yang S, Bayer AS, Vaezzadeh AR, Herzig S, Stenz L, Girard M, Sakoulas G, Scherl A, Yeaman MR, Proctor RA, Schrenzel J, François P |
| Citation(s) |
21622973 |
| |
| Submission date |
Apr 14, 2011 |
| Last update date |
Mar 23, 2012 |
| Contact name |
FRANCOIS Patrice |
| E-mail(s) |
[email protected]
|
| Phone |
+41 (0)22 372 93 37
|
| Organization name |
Genomic Research Laboratory
|
| Department |
Service of Infectious Diseases
|
| Lab |
Genomic Research Lab
|
| Street address |
Rue Gabrielle-Perret-Gentil, 4
|
| City |
Geneva |
| State/province |
Ge 4 |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL7137 |
Agilent-017903 Staphylococcus aureus V5 Bis 15K (basic) |
|
| Samples (6)
|
| GSM709602 |
Daptomycin suceptible strain WT 5 hours growth replicate 1 |
| GSM709603 |
Daptomycin suceptible strain WT 5 hours growth replicate 2 |
| GSM709604 |
Daptomycin suceptible strain WT 5 hours growth replicate 3 |
| GSM709605 |
Daptomycin non-suceptible strain DAPR 5 hours growth replicate 1 |
| GSM709606 |
Daptomycin non-suceptible strain DAPR 5 hours growth replicate 2 |
| GSM709607 |
Daptomycin non-suceptible strain DAPR 5 hours growth replicate 3 |
|
| Relations |
| BioProject |
PRJNA138881 |
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