ArticleAntimicrobial agents and chemotherapy2014
High proportion of heteroresistance in gyrA and gyrB in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled it
- Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis.Annals of clinical microbiology and antimicrobials · 2021Pooled it
- Bacterial heteroresistance mechanisms, dynamics, and emerging diagnostic approaches.Bioscience reports · 2026Review
- Screening for heterogeneous drug resistance in tuberculosis and its impact on clinical prognosis: A comprehensive review.iScience · 2026Review
- Article
- Improved detection of isoniazid-heteroresistantMicrobiology spectrum · 2025Article
- Identification and quantification ofJournal of clinical microbiology · 2025Article
- Investigation of bedaquiline heteroresistance amongMicrobiology spectrum · 2025Article
- Article
- Surveillance of fluoroquinolones resistance in rifampicin-susceptible tuberculosis in eastern China with whole-genome sequencing-based approach.Frontiers in microbiology · 2024Article
- Article
- Quantification of Isoniazid-Heteroresistant Mycobacterium tuberculosis Using Droplet Digital PCR.Journal of clinical microbiology · 2023Article
- Development and Assessment of a Novel Whole-Gene-Based Targeted Next-Generation Sequencing Assay for Detecting the Susceptibility of Mycobacterium tuberculosis to 14 Drugs.Microbiology spectrum · 2022Article
- Ultrasensitive Detection of Multidrug-ResistantInternational journal of molecular sciences · 2022Article
- Highly Sensitive Detection of Isoniazid Heteroresistance inInfection and drug resistance · 2022Article
- Fluoroquinolone heteroresistance, antimicrobial tolerance, and lethality enhancement.Frontiers in cellular and infection microbiology · 2022Review
- Whole-genome sequencing for surveillance of fluoroquinolone resistance in rifampicin-susceptible tuberculosis in a rural district of Shanghai: A 10-year retrospective study.Frontiers in public health · 2022Article
- The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis.FEMS microbiology reviews · 2021Review
- Detection of Pyrazinamide Heteroresistance in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2021Article
- 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
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Heteroresistance is the coexistence of populations with differing nucleotides at a drug resistance locus within a sample of organisms. Although Sanger sequencing is the gold standard for sequencing, it may be less sensitive than deep sequencing for detecting fluoroquinolone heteroresistance in Mycobacterium tuberculosis. Twenty-seven fluoroquinolone monoresistant and 11 fluoroquinolone-susceptible M. tuberculosis isolates were analyzed by Sanger and Illumina deep sequencing. Individual sequencing reads were analyzed to detect heteroresistance in the gyrA and gyrB genes. Heteroresistance to fluoroquinolones was identified in 10/26 (38%) phenotypically fluoroquinolone-resistant samples and 0/11 (P = 0.02) fluoroquinolone-susceptible controls. One resistant sample was excluded because of contamination with the laboratory strain M. tuberculosis H37Rv. Sanger sequencing revealed resistance-conferring mutations in 15 isolates, while deep sequencing revealed mutations in 20 isolates. Isolates with fluoroquinolone resistance-conferring mutations by Sanger sequencing all had at least those same mutations identified by deep sequencing. By deep sequencing, 10 isolates had a single fixed (defined as >95% frequency) mutation, while 10 were heteroresistant, 5 of which had a single unfixed (defined as <95% frequency) mutation and 5 had multiple unfixed mutations. Illumina deep sequencing identified a higher proportion of fluoroquinolone-resistant M. tuberculosis isolates with heteroresistance than did Sanger sequencing. The heteroresistant isolates frequently demonstrated multiple mutations, but resistant isolates with fixed mutations each had only a single mutation.
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