Work

Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance inMycobacterium tuberculosis

Year: 2023

Type: article

Abstract: Objectives 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. Methods 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. Results 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. Conclusions 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.

Source: JAC-Antimicrobial Resistance

DOI: 10.1093/jacamr/dlad039

Authors: Alice E Brankin, Philip W Fowler

Institutions: University of Oxford, John Radcliffe Hospital

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,231