Mode of action analysis: Distinct Staphylococcus aureus transcriptome changes upon antivirulence hydroxy amide treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Staphylococcus aureus
PROVIDER: GSE64747 | GEO | 2016/01/14
SECONDARY ACCESSION(S): PRJNA271787
REPOSITORIES: GEO
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Project description:The common research strain S. aureus NCTC 8325-4 was subjected to serial passage in increasing concentrations of ramoplanin. The resulting strain, RSPA16, had reduced susceptibility to not only ramoplanin but vancomycin and nisin as well. Electron microscopy revealed that the cell wall of RSPA16 was double the thickness of the susceptible progenitor strain, a phenotype commonly observed in vancomycin intermediate resistant S. aureus (VISA) strains. RSPA16 was also less susceptible to lysis induced by Triton X-100 than its progenitor strain. Transcriptional profiling experiments were performed with NCTC 8325-4 and RSPA16 without antibiotic exposure and exposed to ramoplanin. Increased expression of genes associated with cell wall stress was observed when either strain was treated with ramoplanin. We also observed that treatment with ramoplanin altered of the expression levels of numerous genes encoding proteins involved with amino acid biosynthesis, central metabolic pathways, nucleotide biosynthesis, iron acquisition, ABC transporters and regulation of transcription. Comparison of the transcriptional profiles of RSPA16 and NCTC 8325-4 not exposed to ramoplanin revealed alterations in the expression of levels of several genes involved with biosynthesis of teichoic acids, biosynthesis of peptidoglycan, central metabolism, DNA replication, nucleotide biosynthesis, iron acquisition, ABC transporters, and regulation of transcription. These transcriptional profiles provide insights into the possible sources of the reduced susceptibility of RSPA16 to peptide antibiotics.
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Project description:Mode of action analysis: Distinct Staphylococcus aureus transcriptome changes upon antivirulence hydroxy amide treatment
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