ArticleAntimicrobial agents and chemotherapy2012
Extending the definition of the GyrB quinolone resistance-determining region in Mycobacterium tuberculosis DNA gyrase for assessing fluoroquinolone resistance in M. tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Pooled it
- Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis.The Journal of antimicrobial chemotherapy · 2014Pooled it
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- Structural Aspects ofACS medicinal chemistry letters · 2024Article
- Identification of novel resistance-associated mutations and discrimination within whole-genome sequences of fluoroquinolone-resistantMicrobiology spectrum · 2024Article
- Revealing the Interaction Mechanism betweenInternational journal of molecular sciences · 2024Article
- Impacts of MDR/XDR-TB on the global tuberculosis epidemic: Challenges and opportunities.Current research in microbial sciences · 2024Review
- Comparison of theHeliyon · 2023Article
- Distribution of common and rare drug resistance patterns inJournal of thoracic disease · 2023Article
- Predicting antibiotic resistance in complex protein targets using alchemical free energy methods.Journal of computational chemistry · 2022Article
- Genome-wide association studies of global Mycobacterium tuberculosis resistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms.PLoS biology · 2022Article
- Genomic characterization of two metagenome-assembled genomes ofFrontiers in cellular and infection microbiology · 2022Article
- Molecular Surveillance of Antimicrobial Resistance ofInfection and drug resistance · 2022Article
- Resistance-Conferring Mutations on Whole-Genome Sequencing of Fluoroquinolone-resistant and -Susceptible Mycobacterium tuberculosis Isolates: A Proposed Threshold for Identifying Resistance.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Increasing prevalence of resistance to second-line drugs among multidrug-resistant Mycobacterium tuberculosis isolates in Kuwait.Scientific reports · 2021Article
- Computational modeling and bioinformatic analyses of functional mutations in drug target genes inComputational and structural biotechnology journal · 2021Article
- Genomic Analysis of Mycobacterium tuberculosis Isolates and Construction of a Beijing Lineage Reference Genome.Genome biology and evolution · 2020Article
- Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs AmongInfection and drug resistance · 2020Article
- Fluoroquinolone resistance in multidrug-resistant tuberculosis patients.The Korean journal of internal medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoroquinolone (FQ) resistance is emerging in Mycobacterium tuberculosis. The main mechanism of FQ resistance is amino acid substitution within the quinolone resistance-determining region (QRDR) of the GyrA subunit of DNA gyrase, the sole FQ target in M. tuberculosis. However, substitutions in GyrB whose implication in FQ resistance is unknown are increasingly being reported. The present study clarified the role of four GyrB substitutions identified in M. tuberculosis clinical strains, two located in the QRDR (D500A and N538T) and two outside the QRDR (T539P and E540V), in FQ resistance. We measured FQ MICs and also DNA gyrase inhibition by FQs in order to unequivocally clarify the role of these mutations in FQ resistance. Wild-type GyrA, wild-type GyrB, and mutant GyrB subunits produced from engineered gyrB alleles by mutagenesis were overexpressed in Escherichia coli, purified to homogeneity, and used to reconstitute highly active gyrase complexes. MICs and DNA gyrase inhibition were determined for moxifloxacin, gatifloxacin, ofloxacin, levofloxacin, and enoxacin. All these substitutions are clearly implicated in FQ resistance, underlining the presence of a hot spot region housing most of the GyrB substitutions implicated in FQ resistance (residues NTE, 538 to 540). These findings help us to refine the definition of GyrB QRDR, which is extended to positions 500 to 540.
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