Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis
<p><strong>Objectives</strong> Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensiti...
| Main Authors: | , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2023
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| _version_ | 1797110295557046272 |
|---|---|
| author | Brankin, AE Fowler, PW |
| author_facet | Brankin, AE Fowler, PW |
| author_sort | Brankin, AE |
| collection | OXFORD |
| description | <p><strong>Objectives</strong>
Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.</p>
<p><strong>Methods</strong>
We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.</p>
<p><strong>Results</strong>
Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.</p>
<p><strong>Conclusions</strong>
Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.</p> |
| first_indexed | 2024-03-07T07:52:58Z |
| format | Journal article |
| id | oxford-uuid:5fd3b72e-1f5b-4768-8b1b-8f3cf6328d8b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:52:58Z |
| publishDate | 2023 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:5fd3b72e-1f5b-4768-8b1b-8f3cf6328d8b2023-08-02T12:35:02ZInclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5fd3b72e-1f5b-4768-8b1b-8f3cf6328d8bEnglishSymplectic ElementsOxford University Press2023Brankin, AEFowler, PW<p><strong>Objectives</strong> Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.</p> <p><strong>Methods</strong> We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.</p> <p><strong>Results</strong> Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.</p> <p><strong>Conclusions</strong> Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.</p> |
| spellingShingle | Brankin, AE Fowler, PW Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis |
| title | Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis |
| title_full | Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis |
| title_fullStr | Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis |
| title_full_unstemmed | Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis |
| title_short | Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis |
| title_sort | inclusion of minor alleles improves catalogue based prediction of fluoroquinolone resistance in mycobacterium tuberculosis |
| work_keys_str_mv | AT brankinae inclusionofminorallelesimprovescataloguebasedpredictionoffluoroquinoloneresistanceinmycobacteriumtuberculosis AT fowlerpw inclusionofminorallelesimprovescataloguebasedpredictionoffluoroquinoloneresistanceinmycobacteriumtuberculosis |