GyrI: a counter-defensive strategy against proteinaceous inhibitors of DNA gyrase.
DNA gyrase is the target of two plasmid-encoded toxins CcdB and microcin B17, which ensure plasmid maintenance. These proteins stabilize gyrase-DNA covalent complexes leading to double-strand breaks in the genome. In contrast, the physiological role of chromosomally encoded inhibitor of DNA gyrase (GyrI) in Escherichia coli is unclear and its mechanism of inhibition has not been established. We demonstrate that the mode of inhibition of GyrI is distinct from all other gyrase inhibitors. It inhibits DNA gyrase prior to, or at the step of, binding of DNA by the enzyme. GyrI reduces intrinsic as well as toxin-stabilized gyrase-DNA covalent complexes. Furthermore, GyrI reduces microcin B17-mediated double-strand breaks in vivo, imparting protection to the cells against the toxin, substantiating the in vitro results. Thus, GyrI is an antidote to DNA gyrase-specific proteinaceous poisons encoded by plasmid addiction systems.
Chatterji
Monalisa
M
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
Nagaraja
Valakunja
V
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics; D001430:Bacteriocins / Q000235:genetics / Q000494:pharmacology; D004791:Enzyme Inhibitors; D004926:Escherichia coli / Q000201:enzymology / Q000502:physiology*; D029968:Escherichia coli Proteins; D010957:Plasmids; D012097:Repressor Proteins; D059005:Topoisomerase II Inhibitors
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001430:Bacteriocins; C068356:CcdB protein, Plasmid F; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; C110533:SbmC protein, E coli; D059005:Topoisomerase II Inhibitors; C020411:microcin