Response of Staphylococcus aureus to subinhibitory concentrations of a sequence-selective, DNA minor groove cross-linking pyrrolobenzodiazepine dimer.

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 intrast

SUBMITTER: Doyle M 

PROVIDER: S-EPMC2764867 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature