Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential?

G Satta; M Lipman; G P Smith; C Arnold; O M Kon; T D McHugh

doi:10.1016/j.cmi.2017.10.030

Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential?

Clin Microbiol Infect. 2018 Jun;24(6):604-609. doi: 10.1016/j.cmi.2017.10.030. Epub 2017 Nov 3.

Authors

G Satta¹, M Lipman², G P Smith³, C Arnold⁴, O M Kon⁵, T D McHugh⁶

Affiliations

¹ UCL-TB and UCL Centre for Clinical Microbiology, Department of Infection, University College London, UK; Imperial College Healthcare NHS Trust, London, UK. Electronic address: Giovanni.satta@nhs.net.
² UCL-TB and UCL Respiratory, University College London, UK; Royal Free London NHS Foundation Trust, London, UK.
³ National Mycobacterium Reference Laboratory, Public Health England, UK; Heart of England NHS Foundation Trust, Birmingham, UK.
⁴ UCL-TB and UCL Centre for Clinical Microbiology, Department of Infection, University College London, UK; Genomic Services and Development Unit, Public Health England, UK.
⁵ Imperial College Healthcare NHS Trust, London, UK; National Heart and Lung Institute, Imperial College London, UK.
⁶ UCL-TB and UCL Centre for Clinical Microbiology, Department of Infection, University College London, UK.

PMID: 29108952
DOI: 10.1016/j.cmi.2017.10.030

Abstract

Background: Nearly two decades after completion of the genome sequence of Mycobacterium tuberculosis (MTB), and with the advent of next generation sequencing technologies (NGS), whole-genome sequencing (WGS) has been applied to a wide range of clinical scenarios. Starting in 2017, England is the first country in the world to pioneer its use on a national scale for the diagnosis of tuberculosis, detection of drug resistance, and typing of MTB.

Aims: This narrative review critically analyses the current applications of WGS for MTB and explains how close we are to realizing its full potential as a diagnostic, epidemiologic, and research tool.

Sources: We searched for reports (both original articles and reviews) published in English up to 31 May 2017, with combinations of the following keywords: whole-genome sequencing, Mycobacterium, and tuberculosis. MEDLINE, Embase, and Scopus were used as search engines. We included articles that covered different aspects of whole-genome sequencing in relation to MTB.

Content: This review focuses on three main themes: the role of WGS for the prediction of drug susceptibility, MTB outbreak investigation and genetic diversity, and research applications of NGS.

Implications: Many of the original expectations have been accomplished, and we believe that with its unprecedented sensitivity and power, WGS has the potential to address many unanswered questions in the near future. However, caution is still needed when interpreting WGS data as there are some important limitations to be aware of, from correct interpretation of drug susceptibilities to the bioinformatic support needed.

Keywords: Applications; Drug resistance; Mycobacterium tuberculosis; Whole genome sequencing.

Publication types

Review

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacterial Typing Techniques
Disease Outbreaks
Drug Resistance, Bacterial
Genome, Bacterial
High-Throughput Nucleotide Sequencing / methods*
Humans
Mycobacterium tuberculosis / genetics*
Tuberculosis / epidemiology*
Tuberculosis / microbiology
Whole Genome Sequencing / methods*

Substances

Anti-Bacterial Agents