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MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era
- Source :
- Genome Medicine, Genome Medicine, 2020, 12 (1), pp.104. ⟨10.1186/s13073-020-00793-8⟩
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
Abstract
- Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.
- Subjects :
- 0301 basic medicine
MESH: Mycobacterium tuberculosis
Antitubercular Agents
Drug resistance
Multidrug resistance
Disease Outbreaks
Clofazimine
chemistry.chemical_compound
Tuberculosis, Multidrug-Resistant
MESH: Disease Outbreaks
Diarylquinolines
MESH: Bacterial Proteins
Genetics (clinical)
MESH: Microbial Sensitivity Tests
Resistance mutation
MESH: Diarylquinolines
Mycobacterium tuberculosis complex
Molecular Medicine
medicine.drug
MESH: Mutation
Tuberculosis
030106 microbiology
Microbial Sensitivity Tests
Biology
03 medical and health sciences
Bacterial Proteins
MESH: Eswatini
Genetics
medicine
Humans
Molecular Biology
MESH: Tuberculosis, Multidrug-Resistant
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
Diagnostice escape
Research
MESH: Clone Cells
Resistance evolution
Treatment escape
Mycobacterium tuberculosis
rpoB
medicine.disease
biology.organism_classification
MESH: Antitubercular Agents
Virology
Clone Cells
Multiple drug resistance
MDR outbreak strains
030104 developmental biology
chemistry
Treatment failure
Mutation
Bedaquiline
Eswatini
Subjects
Details
- Language :
- English
- ISSN :
- 1756994X
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Genome Medicine
- Accession number :
- edsair.doi.dedup.....3638cc6199751d5d5fb8e81135399998