ArticleBMC microbiology2012
Sequence analysis for detection of first-line drug resistance in Mycobacterium tuberculosis strains from a high-incidence setting.
Article in BMC microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates.Antimicrobial agents and chemotherapy · 2015Pooled it
- Frequency, genetic mechanisms and factors associated with fluoroquinolone (pre-XDR) and aminoglycoside resistance among multidrug-resistant tuberculosis cases in Northwestern Nigeria.BMC infectious diseases · 2026Article
- Investigation of Gene Regions Responsible for Drug Resistance in Clinical Isolates ofPathogens (Basel, Switzerland) · 2026Article
- Molecular epidemiology of drug resistance and transmission ofMicrobiology spectrum · 2026Article
- Discovery of pyrimidine-tethered benzothiazole derivatives as novel anti-tubercular agents towards multi- and extensively drug resistantJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Operationalising targeted next-generation sequencing for routine diagnosis of drug-resistant TB.Public health action · 2023Article
- Distribution ofTropical medicine and infectious disease · 2022Article
- Characterization of Genetic Variants Associated with Rifampicin Resistance Level inInfection and drug resistance · 2022Article
- Review
- Should treatment of low-level rifampicin mono-resistant tuberculosis be different?Journal of clinical tuberculosis and other mycobacterial diseases · 2021Article
- Frequency of Codon 306 Mutations inInternational journal of preventive medicine · 2020Review
- Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-ResistantInfection and drug resistance · 2020Article
- A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis.Scientific reports · 2019Article
- The roles ofInternational journal of clinical and experimental pathology · 2019Article
- Potential impact of efflux pump genes in mediating rifampicin resistance in clinical isolates of Mycobacterium tuberculosis from India.PloS one · 2019Article
- Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase.Scientific reports · 2018Article
- Characterization of Mutations Conferring Resistance to Rifampin in Mycobacterium tuberculosis Clinical Strains.Antimicrobial agents and chemotherapy · 2018Article
- Correlation between the BACTEC MGIT 960 culture system with Genotype MTBDRplus and TB-SPRINT in multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil.Memorias do Instituto Oswaldo Cruz · 2017Article
- Revisiting the mutant prevention concentration to guide dosing in childhood tuberculosis.The Journal of antimicrobial chemotherapy · 2017Review
- Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State.Journal of clinical microbiology · 2017Article
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7 authors.
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Abstract
backgroundDrug resistance displays a problem for the therapy of Mycobacterium tuberculosis infections. For molecular resistance testing, it is essential to have precise knowledge on genomic variations involved in resistance development. However, data from high-incidence settings are only sparely available. Therefore we performed a systematic approach and analyzed a total of 97 M. tuberculosis strains from previously treated patients in Sierra Leone for mutations in katG, rpoB, rrs, rpsL, gidB, embB, pncA and where applicable in inhA and ahpC. Of the strains investigated 50 were either mono- or poly-resistant to isoniazid, rifampin, streptomycin, ethambutol and pyrazinamide or MDR and 47 fully susceptible strains served as controls.
resultsThe majority of isoniazid and rifampin resistant strains had mutations in katG315 (71.9%) and rpoB531 (50%). However, rpoB mutations in codons 511, 516 and 533 were also detected in five rifampin susceptible strains. MIC determinations revealed low-level rifampin resistance for those strains. Thus, the sensitivity and specificity of sequencing of katG for detection of drug resistance were 86.7% and 100% and for sequencing of rpoB 100% and 93.8%, respectively.Strikingly, none of the streptomycin resistant strains had mutations in rrs, but 47.5% harboured mutations in rpsL. Further changes were detected in gidB. Among ethambutol resistant strains 46.7% had mutations at embB306. Pyrazinamide resistant strains displayed a variety of mutations throughout pncA. The specificities of sequencing of rpsL, embB and pncA for resistance detection were high (96-100%), whereas sensitivities were lower (48.8%, 73.3%, 70%).
conclusionsOur study reveals a good correlation between data from molecular and phenotypic resistance testing in this high-incidence setting. However, the fact that particular mutations in rpoB are not linked to high-level resistance is challenging and demonstrates that careful interpretation of molecular resistance assays is mandatory. In addition, certain variations, especially in gidB, appear to be phylogenetically informative polymorphisms rather than markers for drug resistance.
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