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Tuberculosis (Edinb). 2019 Mar;115:81-88. doi: 10.1016/j.tube.2019.02.006. Epub 2019 Feb 25.

Evaluation of a gene-by-gene approach for prospective whole-genome sequencing-based surveillance of multidrug resistant Mycobacterium tuberculosis.

Author information

1
National Reference Laboratory for Mycobacteria, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: rita.macedo@insa.min-saude.pt.
2
Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: miguel.pinto@insa.min-saude.pt.
3
Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: vitor.borges@insa.min-saude.pt.
4
Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: alexandra.nunes@insa.min-saude.pt.
5
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; ICVS/3B, PT Government Associate Laboratory, 4710-057, Braga/4805-017, Guimar√£es, Portugal; EPI Unit, Institute of Public Health, University of Porto, 4050-600 Porto, Portugal. Electronic address: radomoliveira@gmail.com.
6
iMed.ULisboa-Research Institute for Medicines, University of Lisbon, Lisbon, Portugal. Electronic address: iportugal@ff.ulisboa.pt.
7
EPI Unit, Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; Clinical Epidemiology, Predictive Medicine and Public Health Department, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho EPE, 4400-129 Vila Nova de Gaia, Portugal. Electronic address: raquelafduarte@gmail.com.
8
Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: j.paulo.gomes@insa.min-saude.pt.

Abstract

Whole-genome sequencing (WGS) offers unprecedented resolution for tracking Mycobacterium tuberculosis transmission and antibiotic-resistance spread. Still, the establishment of standardized WGS-based pipelines and the definition of epidemiological clusters based on genetic relatedness are under discussion. We aimed to implement a dynamic gene-by-gene approach, fully relying on freely available software, for prospective WGS-based tuberculosis surveillance, demonstrating its application for detecting transmission chains by retrospectively analysing all M/XDR strains isolated in 2013-2017 in Portugal. We observed a good correlation between genetic relatedness and epidemiological links, with strongly epilinked clusters displaying mean pairwise allele differences (AD) always below 0.3% (ratio of mean AD over the total number of shared loci between same-cluster strains). This data parallels the genetic distances acquired by the core-SNV analysis, while providing higher resolution and epidemiological concordance than MIRU-VNTR genotyping. The dynamic analysis of strain sub-sets (i.e., increasing the number of shared loci within each sub-set) also strengthens the confidence in detecting epilinked clusters. This gene-by-gene strategy also offers several practical benefits (e.g., reliance on freely-available software, scalability and low computational requirements) that further consolidated its suitability for a timely and robust prospective WGS-based laboratory surveillance of M/XDR-TB cases.

KEYWORDS:

Gene-by-gene approach; Multidrug-resistance; Mycobacterium tuberculosis; Surveillance; Whole-genome sequencing

PMID:
30948181
DOI:
10.1016/j.tube.2019.02.006

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