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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Macedo, R (Author) Other; Pinto, M (Author) Other; Borges, V (Author) Other; Nunes, A (Author) Other; Oliveira, O (Author) Other; Portugal, I (Author) Other; Duarte R (Author) Other; Gomes, JP (Author) Other

Journal

Title: Tuberculosis

Vol. 115

Pages: 81-88

ISSN: 1472-9792

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-00Q-98J

DOI: 10.1016/j.tube.2019.02.006

Abstract (EN): 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 subsets (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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8