| Literature DB >> 30778225 |
Priyanka Kachroo1, Jesus M Eraso1, Stephen B Beres1, Randall J Olsen1,2,3, Luchang Zhu1, Waleed Nasser1, Paul E Bernard1, Concepcion C Cantu1, Matthew Ojeda Saavedra1, María José Arredondo1, Benjamin Strope1, Hackwon Do1, Muthiah Kumaraswami1, Jaana Vuopio4,5, Kirsi Gröndahl-Yli-Hannuksela4, Karl G Kristinsson6,7, Magnus Gottfredsson7,8, Maiju Pesonen9,10, Johan Pensar9, Emily R Davenport11, Andrew G Clark11, Jukka Corander9,12, Dominique A Caugant13, Shahin Gaini14,15,16,17, Marita Debess Magnussen7,18, Samantha L Kubiak1, Hoang A T Nguyen1, S Wesley Long1, Adeline R Porter19, Frank R DeLeo19, James M Musser20,21,22.
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.Entities:
Mesh：
Year: 2019 PMID： 30778225 PMCID： PMC8547240 DOI： 10.1038/s41588-018-0343-1
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330