Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis

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

doi:10.1038/s41588-018-0343-1

Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis

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

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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.

Original language	English (US)
Pages (from-to)	548-559
Number of pages	12
Journal	Nature Genetics
Volume	51
Issue number	3
DOIs	https://doi.org/10.1038/s41588-018-0343-1
State	Published - Mar 1 2019

All Science Journal Classification (ASJC) codes

Genetics

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Kachroo, P., Eraso, J. M., Beres, S. B., Olsen, R. J., Zhu, L., Nasser, W., Bernard, P. E., Cantu, C. C., Saavedra, M. O., Arredondo, M. J., Strope, B., Do, H., Kumaraswami, M., Vuopio, J., Gröndahl-Yli-Hannuksela, K., Kristinsson, K. G., Gottfredsson, M., Pesonen, M., Pensar, J., ... Musser, J. M. (2019). Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis. Nature Genetics, 51(3), 548-559. https://doi.org/10.1038/s41588-018-0343-1

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title = "Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis",

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.",

author = "Priyanka Kachroo and Eraso, {Jesus M.} and Beres, {Stephen B.} and Olsen, {Randall J.} and Luchang Zhu and Waleed Nasser and Bernard, {Paul E.} and Cantu, {Concepcion C.} and Saavedra, {Matthew Ojeda} and Arredondo, {Mar{\'i}a Jos{\'e}} and Benjamin Strope and Hackwon Do and Muthiah Kumaraswami and Jaana Vuopio and Kirsi Gr{\"o}ndahl-Yli-Hannuksela and Kristinsson, {Karl G.} and Magnus Gottfredsson and Maiju Pesonen and Johan Pensar and Davenport, {Emily R.} and Clark, {Andrew G.} and Jukka Corander and Caugant, {Dominique A.} and Shahin Gaini and Magnussen, {Marita Debess} and Kubiak, {Samantha L.} and Nguyen, {Hoang A.T.} and Long, {S. Wesley} and Porter, {Adeline R.} and DeLeo, {Frank R.} and Musser, {James M.}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = mar,

day = "1",

doi = "10.1038/s41588-018-0343-1",

language = "English (US)",

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pages = "548--559",

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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, Kristinsson, KG, Gottfredsson, M, Pesonen, M, Pensar, J, Davenport, ER, Clark, AG, Corander, J, Caugant, DA, Gaini, S, Magnussen, MD, Kubiak, SL, Nguyen, HAT, Long, SW, Porter, AR, DeLeo, FR & Musser, JM 2019, 'Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis', Nature Genetics, vol. 51, no. 3, pp. 548-559. https://doi.org/10.1038/s41588-018-0343-1

TY - JOUR

T1 - Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis

AU - Kachroo, Priyanka

AU - Eraso, Jesus M.

AU - Beres, Stephen B.

AU - Olsen, Randall J.

AU - Zhu, Luchang

AU - Nasser, Waleed

AU - Bernard, Paul E.

AU - Cantu, Concepcion C.

AU - Saavedra, Matthew Ojeda

AU - Arredondo, María José

AU - Strope, Benjamin

AU - Do, Hackwon

AU - Kumaraswami, Muthiah

AU - Vuopio, Jaana

AU - Gröndahl-Yli-Hannuksela, Kirsi

AU - Kristinsson, Karl G.

AU - Gottfredsson, Magnus

AU - Pesonen, Maiju

AU - Pensar, Johan

AU - Davenport, Emily R.

AU - Clark, Andrew G.

AU - Corander, Jukka

AU - Caugant, Dominique A.

AU - Gaini, Shahin

AU - Magnussen, Marita Debess

AU - Kubiak, Samantha L.

AU - Nguyen, Hoang A.T.

AU - Long, S. Wesley

AU - Porter, Adeline R.

AU - DeLeo, Frank R.

AU - Musser, James M.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41588-018-0343-1

DO - 10.1038/s41588-018-0343-1

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AN - SCOPUS:85060887096

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VL - 51

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JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis

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