Fig. 4: Genome studies reveal DNA gyrase as a target. | Nature Chemistry

Fig. 4: Genome studies reveal DNA gyrase as a target.

From: Discovery of isoquinoline sulfonamides as allosteric gyrase inhibitors with activity against fluoroquinolone-resistant bacteria

Fig. 4

a, Agar containing 60 (5× MIC) was inoculated with 107 c.f.u. of E. coli. After 1 day, nine viable colonies were isolated and used for MIC testing and WGS. b, Susceptibility assays confirm spontaneous resistance to 60 and WGS identified mutations located in the DNA gyrase, predominantly in subunit A. Similar mutations are similarly coloured. Cross-resistance is observed for conformationally restricted compounds 101 and LEI-800. c, Localization of the mutations in the core of the DNA gyrase heterotetramer (PDB: 6RKW) outline a possible binding site of isoquinoline sulfonamides. d, All mutations are found in the cleavage-reunion domain of DNA gyrase. Domain organization of DNA gyrase, GyrB (coral) and GyrA (beige) subunits.

Back to article page