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

Macedo, Rita; Pinto, Miguel; Borges, Vítor; Nunes, Alexandra; Oliveira, Olena; Portugal, Isabel; Duarte, Raquel; Gomes, João Paulo

http://hdl.handle.net/10400.18/6500

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Abstract(s)

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.

Description

Supplementary data to this article can be found online at https:// doi.org/10.1016/j.tube.2019.02.006.

Keywords

Genes, Bacterial Genome, Bacterial Genotype Humans Mycobacterium tuberculosis Phylogeny Polymorphism, Single Nucleotide Portugal Prospective Studies Tuberculosis, Multidrug-Resistant Whole Genome Sequencing Infecções Respiratórias