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Genotypic characterization of 'inferred' rifampin mutations in GenoType MTBDRplus assay and its association with phenotypic susceptibility testing of Mycobacterium tuberculosis.
- Source :
-
Diagnostic microbiology and infectious disease [Diagn Microbiol Infect Dis] 2020 Apr; Vol. 96 (4), pp. 114995. Date of Electronic Publication: 2020 Jan 23. - Publication Year :
- 2020
-
Abstract
- In GenoType MTBDRplus assay [line probe assay (LPA)], when Mycobacterium tuberculosis (M. tuberculosis) sample DNA fails to hybridize to at least 1 rpoB wild-type probe and any mutation probe, it is inferred as rifampin (RIF)-resistant. In this study, we sought to identify such 'inferred' mutations in M. tuberculosis isolates (n = 203) by rpoB gene sequencing and determined their association with phenotypic resistance. D516Y, H526N, L511P mutations were associated with both phenotypically sensitive (59%, n = 38/64) and resistant (23.7%, n = 33/139) antimicrobial susceptibility testing (AST) results, whereas S531W mutation was associated with only RIF-resistant isolates (33%, n = 46/139). These results demonstrated that, at standard drug concentrations, some 'inferred' mutations may be missed by RIF-AST (phenotypically sensitive). The use of LPA permits identification of these RIF-resistant isolates, and incorporation of additional mutation probes (e.g., S531W) could further increase LPA specificity. Further studies are needed to establish the significance of the type of 'inferred' mutation with clinical/treatment outcomes.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Bacterial Proteins genetics
DNA-Directed RNA Polymerases genetics
Genotype
Humans
Microbial Sensitivity Tests
Phenotype
Sputum microbiology
Tuberculosis microbiology
Antitubercular Agents pharmacology
Drug Resistance, Multiple, Bacterial genetics
Mutation
Mycobacterium tuberculosis drug effects
Rifampin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0070
- Volume :
- 96
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Diagnostic microbiology and infectious disease
- Publication Type :
- Academic Journal
- Accession number :
- 32037037
- Full Text :
- https://doi.org/10.1016/j.diagmicrobio.2020.114995