TY - JOUR
T1 - Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences
AU - Nasser, Waleed
AU - Beres, Stephen B.
AU - Olsen, Randall J.
AU - Dean, Melissa A.
AU - Rice, Kelsey A.
AU - Long, S. Wesley
AU - Kristinsson, Karl G.
AU - Gottfredsson, Magnus
AU - Vuopio, Jaana
AU - Raisanen, Kati
AU - Caugant, Dominique A.
AU - Steinbakk, Martin
AU - Low, Donald E.
AU - McGeer, Allison
AU - Darenberg, Jessica
AU - Henriques-Normark, Birgitta
AU - Van Beneden, Chris A.
AU - Hoffmann, Steen
AU - Musser, James M.
PY - 2014/4/29
Y1 - 2014/4/29
N2 - We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion froma precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD+-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population- based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.
AB - We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion froma precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD+-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population- based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.
KW - Flesh-eating disease
KW - Mobile genetic element
KW - Molecular clock
KW - Pathogenesis
KW - Phylogeography
UR - http://www.scopus.com/inward/record.url?scp=84899645046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899645046&partnerID=8YFLogxK
U2 - 10.1073/pnas.1403138111
DO - 10.1073/pnas.1403138111
M3 - Article
C2 - 24733896
AN - SCOPUS:84899645046
SN - 0027-8424
VL - 111
SP - E1768-E1776
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -