Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis. Academic Article uri icon

Overview

abstract

  • 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.

authors

  • Kachroo, Priyanka
  • Eraso, Jesus M
  • Beres, Stephen B
  • Olsen, Randall
  • Zhu, Luchang
  • Nasser, Waleed
  • Bernard, Paul E
  • Cantu, Concepcion C
  • Saavedra, Matthew Ojeda
  • Arredondo, María José
  • Strope, Benjamin
  • Do, Hackwon
  • Kumaraswami, Muthiah
  • Vuopio, Jaana
  • Gröndahl-Yli-Hannuksela, Kirsi
  • Kristinsson, Karl G
  • Gottfredsson, Magnus
  • Pesonen, Maiju
  • Pensar, Johan
  • Davenport, Emily R
  • Clark, Andrew G
  • Corander, Jukka
  • Caugant, Dominique A
  • Gaini, Shahin
  • Magnussen, Marita Debess
  • Kubiak, Samantha L
  • Nguyen, Hoang A T
  • Long, Scott
  • Porter, Adeline R
  • DeLeo, Frank R
  • Musser, James Mallory

publication date

  • February 18, 2019

Research

keywords

  • Genome, Bacterial
  • Streptococcus pyogenes
  • Transcriptome
  • Virulence

Identity

PubMed Central ID

  • PMC8547240

Scopus Document Identifier

  • 85060887096

Digital Object Identifier (DOI)

  • 10.1038/s41588-018-0343-1

PubMed ID

  • 30778225

Additional Document Info

volume

  • 51

issue

  • 3