DNA gyrase catalyses the adenosine triphosphate-dependent introduction of negative supercoils into DNA. The enzyme binds a DNA-segment at the so-called DNA-gate and cleaves both DNA strands. DNA extending from the DNA-gate is bound at the perimeter of the cylindrical C-terminal domains (CTDs) of the GyrA subunit. The CTDs are believed to contribute to the wrapping of DNA around gyrase in a posi...

Abstract DNA gyrase, a type II topoisomerase found predominantly in bacteria, is the target for variety of ‘poisons’, namely natural product toxins (e.g. albicidin, microcin B17) and clinically important synthetic molecules fluoroquinolones). Resistance to both groups can be mediated by pentapeptide repeat proteins (PRPs). Despite long-term studies, mechanism action these protective PRPs not kn...

An intein-based positive genetic selection system was developed to study protein splicing and to provide a selection system with the potential for finding splicing inhibitors. Inteins can be novel antimicrobial targets when present in essential proteins since blocking splicing would kill the organism. For example, pathogenic mycobacteria encode inteins that interrupt DNA gyrase. The gyrase sele...

Bacterial pathogens such as Staphylococcus aureus undergo major physiological changes when they infect their hosts, requiring the coordinated regulation of gene expression in response to the stresses encountered. Several environmental factors modify the expression of S. aureus virulence genes. This report shows that the expression of spa (virulence gene encoding the cell-wall-associated protein...

Quinolones are a large and widely consumed class of synthetic drugs. Expanded-spectrum quinolones, like ciprofloxacin are highly effective against Gram-negative bacteria, especially Escherichia coli. In E. coli the major target for quinolones is DNA gyrase. This enzyme is composed of two subunits, GyrA and GyrB encoding by gyrA and gyrB, respectively. Mutations in either of these genes cause qu...

In prokaryotes, DNA supercoiling regulates the expression of many genes; for example, the expression of Klebsiella pneumoniae nifLA operon depends on DNA negative supercoiling in anaerobically grown cells, which indicates that DNA supercoiling might play a role in gene regulation of the anaerobic response. Since the expression of the nifH promoter in Sinorhizobium meliloti is not repressed by o...

The aim of this study was to determine whether alternative resistance mechanisms, other than mutation in the quinolone resistance-determining region (QRDR) of DNA gyrase, could confer fluoroquinolone resistance in Clostridium difficile. An in vitro-generated C. difficile mutant exhibiting increased fluoroquinolone resistance was isolated through antibiotic selection on ciprofloxacin. The QRDR o...