A1 Refereed original research article in a scientific journal
Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis
Authors: Kachroo P, Eraso JM, Beres SB, Olsen RJ, Zhu L, Nasser W, Bernard PE, Cantu CC, Saavedra MO, Arredondo MJ, Strope B, Do H, Kumaraswami M, Vuopio J, Gröndahl-Yli-Hannuksela K, Gottfredsson M, Kristinsson KG, Pensar J, Pesonen M, Clark AG, Davenport ER, Caugant DA, Corander J, Magnussen MD, Gaini S, Nguyen HAT, Kubiak SL, Porter AR, Long SW, Musser JM, DeLeo FR
Publisher: Nature Publishing group
Publication year: 2019
Journal: Nature Genetics
Journal name in source: Nature genetics
Journal acronym: Nat Genet
Volume: 51
Issue: 3
First page : 548
Last page: 559
Number of pages: 15
ISSN: 1061-4036
eISSN: 1546-1718
DOI: https://doi.org/10.1038/s41588-018-0343-1
Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens.
