Response of Staphylococcus aureus to subinhibitory concentrations of a sequence-selective, DNA minor groove cross-linking pyrrolobenzodiazepine dimer.
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ABSTRACT: Objectives ELB-21 is a pyrrolo[2,1-c][1,4]benzodiazepine dimer with potent antistaphylococcal activity; it binds covalently to guanine residues on opposing strands of duplex DNA, interfering with regulatory proteins and transcription elongation in a sequence-selective manner. Transcriptional and proteomic alterations induced by exposure of Staphylococcus aureus clinical isolate EMRSA-16 to ELB-21 were determined in order to define more precisely the bactericidal mechanism of the drug. Methods DNase I footprinting was used to identify high-affinity DNA binding sites. Microarrays and gel electrophoresis were used to assess the ELB-21-induced phenotype. Results High-affinity interstrand binding sites in which guanine residues were separated by 4 bp, and also some intrastrand cross-linking sit
ORGANISM(S): Staphylococcus aureus
SUBMITTER: Marie Doyle
PROVIDER: E-BUGS-79 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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