TY - JOUR
T1 - Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus
AU - Olsen, Randall J.
AU - Laucirica, Daniel R.
AU - Watkins, M. Ebru
AU - Feske, Marsha L.
AU - Garcia-Bustillos, Jesus R.
AU - Vu, Chau
AU - Cantu, Concepcion
AU - Shelburne, Samuel
AU - Fittipaldi, Nahuel
AU - Kumaraswami, Muthiah
AU - Shea, Patrick R.
AU - Flores, Anthony R.
AU - Beres, Stephen B.
AU - Lovgren, Maguerite
AU - Tyrrell, Gregory J.
AU - Efstratiou, Androulla
AU - Low, Donald E.
AU - Van Beneden, Chris A.
AU - Musser, James M.
N1 - Funding Information:
Acknowledgments. We thank Dr Bernard W. Beall for assistance with the Active Bacterial Core surveillance (ABCs) strain collection. Financial support. This work was supported in part by the American Heart Association (grant AHA0775045). Potential conflicts of interest. All authors: no reported conflicts All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Whole-genome sequencing of serotype M3 group A streptococci (GAS) from oropharyngeal and invasive infections in Ontario recently showed that the gene encoding regulator of protease B (RopB) is highly polymorphic in this population. To test the hypothesis that ropB is under diversifying selective pressure among all serotype M3 GAS strains, we sequenced this gene in 1178 strains collected from different infection types, geographic regions, and time periods. The results confirmed our hypothesis and discovered a significant association between mutant ropB alleles, decreased activity of its major regulatory target SpeB, and pharyngitis. Additionally, isoallelic strains with ropB polymorphisms were significantly less virulent in a mouse model of necrotizing fasciitis. These studies provide a model strategy for applying whole-genome sequencing followed by deep single-gene sequencing to generate new insight to the rapid evolution and virulence regulation of human pathogens.
AB - Whole-genome sequencing of serotype M3 group A streptococci (GAS) from oropharyngeal and invasive infections in Ontario recently showed that the gene encoding regulator of protease B (RopB) is highly polymorphic in this population. To test the hypothesis that ropB is under diversifying selective pressure among all serotype M3 GAS strains, we sequenced this gene in 1178 strains collected from different infection types, geographic regions, and time periods. The results confirmed our hypothesis and discovered a significant association between mutant ropB alleles, decreased activity of its major regulatory target SpeB, and pharyngitis. Additionally, isoallelic strains with ropB polymorphisms were significantly less virulent in a mouse model of necrotizing fasciitis. These studies provide a model strategy for applying whole-genome sequencing followed by deep single-gene sequencing to generate new insight to the rapid evolution and virulence regulation of human pathogens.
UR - http://www.scopus.com/inward/record.url?scp=84861033764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861033764&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir825
DO - 10.1093/infdis/jir825
M3 - Article
C2 - 22262791
AN - SCOPUS:84861033764
SN - 0022-1899
VL - 205
SP - 1719
EP - 1729
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -