Whole genome sequencing of drug-resistant Mycobacterium tuberculosis isolates in Victoria, Australia

Thinley Dorji; Kristy Horan; Norelle L Sherry; Ee Laine Tay; Maria Globan; Linda Viberg; Katherine Bond; Justin T Denholm; Benjamin P Howden; Patiyan Andersson

doi:10.1016/j.ijid.2023.11.010

Whole genome sequencing of drug-resistant Mycobacterium tuberculosis isolates in Victoria, Australia

Int J Infect Dis. 2024 Jan:138:46-53. doi: 10.1016/j.ijid.2023.11.010. Epub 2023 Nov 14.

Authors

Affiliations

¹ Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
² Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
³ Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia; Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
⁴ Communicable Disease Epidemiology and Surveillance, Health Protection Branch, Public Health Division, Department of Health, Melbourne, Australia.
⁵ Mycobacterium Reference Laboratory, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
⁶ Mycobacterium Reference Laboratory, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia; Royal Melbourne Hospital, Melbourne, Australia.
⁷ Royal Melbourne Hospital, Melbourne, Australia; Victorian Tuberculosis Program. Melbourne Health at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia; Department of Infectious Diseases at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
⁸ Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia; Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia; Centre for Pathogen Genomics, University of Melbourne, Australia. Electronic address: bhowden@unimelb.edu.au.

PMID: 37967715
DOI: 10.1016/j.ijid.2023.11.010

Abstract

Objectives: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance.

Methods: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context.

Results: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs.

Conclusion: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies.

Keywords: Australia; Genomic epidemiology; MDR-TB; Multi-drug resistant tuberculosis; Transmission networks.

MeSH terms

Antitubercular Agents / pharmacology
Antitubercular Agents / therapeutic use
Drug Resistance, Multiple, Bacterial / genetics
Humans
Isoniazid / pharmacology
Isoniazid / therapeutic use
Microbial Sensitivity Tests
Mutation
Mycobacterium tuberculosis*
Phylogeny
Retrospective Studies
Tuberculosis, Multidrug-Resistant* / drug therapy
Tuberculosis, Multidrug-Resistant* / epidemiology
Tuberculosis, Multidrug-Resistant* / microbiology
Victoria / epidemiology
Whole Genome Sequencing

Substances

Antitubercular Agents
Isoniazid