Open AccessNybomycin Inhibits both Fluoroquinolone-Sensitive and Fluoroquinolone-Resistant Escherichia coli DNA Gyrase
Author(s) -
Dmitrii I. Shiriaev,
Alina A. Sofronova,
Ekaterina A. Berdnikovich,
Dmitrii A. Lukianov,
Ekaterina S. Komarova,
V. I. Marina,
Yu. V. Zakalyukina,
Mikhail V. Biryukov,
Tinashe P. Maviza,
Yan A. Ivanenkov,
Петр В. Сергиев,
Ilya А. Osterman,
Olga А. Dontsova
Publication year - 2021
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00777-20
Subject(s) - dna gyrase , topoisomerase , topoisomerase iv , escherichia coli , microbiology and biotechnology , dna , antibiotics , ofloxacin , topoisomerase inhibitor , biology , enterobacteriaceae , gene , genetics , ciprofloxacin
Bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, are targets of many antibiotics including fluoroquinolones (FQs). Unfortunately, a number of bacterial species easily acquire resistance to FQs by mutations in either DNA gyrase or topoisomerase IV genes. The emergence of resistant pathogenic strains is a global problem in healthcare, therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery. An attractive class of compounds is nybomycins, reported to be "reverse antibiotics" that selectively inhibit growth of some Gram-positive FQ-resistant bacteria by targeting the mutant form of DNA gyrase, while being inactive against wild-type strains with FQ-sensitive gyrases. The strong "reverse" effect was demonstrated only for a few Gram-positive organisms resistant to FQs due to the S83L/I mutation in GyrA subunit of DNA gyrase. However, the activity of nybomycins has not been extensively explored among Gram-negative species. Here, we observed that in Gram-negative E. coli ΔtolC strain with enhanced permeability, wild-type gyrase and GyrA S83L mutant, resistant to fluoroquinolones, are both similarly sensitive to nybomycin.