ArticleMolecular biology and evolution2020
The Genetic Background Modulates the Evolution of Fluoroquinolone-Resistance in Mycobacterium tuberculosis.
Article in Molecular biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 57 citations in OpenAlex.
- Resistance potentiators: Evolutionary catalysts of antibiotic resistance.PLoS biology · 2026Article
- Assessing the efficacy of combined treatment using bedaquiline against clinical isolates of multidrug-resistant Mycobacterium tuberculosis in vitro and the macrophage model.BMC microbiology · 2026Article
- Exploring Novel Gene Mutations Associated with Fluoroquinolone Resistance inInfection and drug resistance · 2026Article
- Development of a point-of-care dual one-step recombinase-aided PCR assay for rapid identification ofFrontiers in microbiology · 2026Article
- Fluoroquinolone resistance and mutation profiles inFrontiers in public health · 2026Article
- Article
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Impact of sublineage diversity on intrinsic susceptibility of Beijing genotype Mycobacterium tuberculosis.Annals of clinical microbiology and antimicrobials · 2025Article
- Advantages of updated WHO mutation catalog combined with existing whole-genome sequencing-based approaches for Mycobacterium tuberculosis resistance prediction.Genome medicine · 2025Article
- Quinolone scaffolds as potential drug candidates against infectious microbes: a review.Molecular diversity · 2025Review
- Within-host population dynamics of extensively drug-resistantEvolution, medicine, and public health · 2025Article
- Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China.Frontiers in public health · 2025Article
- Empowering tuberculosis genomic surveillance in Limpopo, South Africa through capacity building.Frontiers in public health · 2025Article
- Mycobacterium smegmatis MfpC is a GEF that regulates mfpA translationally to alter the fluoroquinolone efficacy.Communications biology · 2024Article
- Surveillance of fluoroquinolones resistance in rifampicin-susceptible tuberculosis in eastern China with whole-genome sequencing-based approach.Frontiers in microbiology · 2024Article
- Genetic diversity, evolution and drug resistance ofFrontiers in microbiology · 2024Review
- Opinion review of drug resistant tuberculosis in West Africa: tackling the challenges for effective control.Frontiers in public health · 2024Review
- Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes.Molecular biology and evolution · 2023Article
- The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot.Nature communications · 2023Article
- Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.The Lancet. Infectious diseases · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoroquinolones (FQ) form the backbone in experimental treatment regimens against drug-susceptible tuberculosis. However, little is known on whether the genetic variation present in natural populations of Mycobacterium tuberculosis (Mtb) affects the evolution of FQ-resistance (FQ-R). To investigate this question, we used nine genetically distinct drug-susceptible clinical isolates of Mtb and measured their frequency of resistance to the FQ ofloxacin (OFX) in vitro. We found that the Mtb genetic background led to differences in the frequency of OFX-resistance (OFX-R) that spanned two orders of magnitude and substantially modulated the observed mutational profiles for OFX-R. Further, in vitro assays showed that the genetic background also influenced the minimum inhibitory concentration and the fitness effect conferred by a given OFX-R mutation. To test the clinical relevance of our in vitro work, we surveyed the mutational profile for FQ-R in publicly available genomic sequences from clinical Mtb isolates, and found substantial Mtb lineage-dependent variability. Comparison of the clinical and the in vitro mutational profiles for FQ-R showed that 51% and 39% of the variability in the clinical frequency of FQ-R gyrA mutation events in Lineage 2 and Lineage 4 strains, respectively, can be attributed to how Mtb evolves FQ-R in vitro. As the Mtb genetic background strongly influenced the evolution of FQ-R in vitro, we conclude that the genetic background of Mtb also impacts the evolution of FQ-R in the clinic.
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