Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus

Randall J. Olsen; Daniel R. Laucirica; M. Ebru Watkins; Marsha L. Feske; Jesus R. Garcia-Bustillos; Chau Vu; Concepcion Cantu; Samuel A. Shelburne; Nahuel Fittipaldi; Muthiah Kumaraswami; Patrick R. Shea; Anthony R. Flores; Stephen B. Beres; Maguerite Lovgren; Gregory J. Tyrrell; Androulla Efstratiou; Donald E. Low; Chris A. Van Beneden; James M. Musser

doi:10.1093/infdis/jir825

Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus

Randall J. Olsen^*
, Daniel R. Laucirica
, M. Ebru Watkins
, Marsha L. Feske
, Jesus R. Garcia-Bustillos
, Chau Vu
, Concepcion Cantu
, Samuel A. Shelburne
, Nahuel Fittipaldi
, Muthiah Kumaraswami
, Patrick R. Shea
, Anthony R. Flores
, Stephen B. Beres
, Maguerite Lovgren
, Gregory J. Tyrrell
, Androulla Efstratiou
, Donald E. Low
, Chris A. Van Beneden
, James M. Musser

^*Corresponding author for this work

Colindale RSD Ops

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1719-1729
Number of pages	11
Journal	Journal of Infectious Diseases
Volume	205
Issue number	11
DOIs	https://doi.org/10.1093/infdis/jir825
Publication status	Published - 1 Jun 2012

Bibliographical note

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1093/infdis/jir825

Cite this

Olsen, R. J., Laucirica, D. R., Watkins, M. E., Feske, M. L., Garcia-Bustillos, J. R., Vu, C., Cantu, C., Shelburne, S. A., Fittipaldi, N., Kumaraswami, M., Shea, P. R., Flores, A. R., Beres, S. B., Lovgren, M., Tyrrell, G. J., Efstratiou, A., Low, D. E., Van Beneden, C. A., & Musser, J. M. (2012). Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus. Journal of Infectious Diseases, 205(11), 1719-1729. https://doi.org/10.1093/infdis/jir825

@article{fc68d86d274c410b9f55772916059b2a,

title = "Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus",

abstract = "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.",

author = "Olsen, \{Randall J.\} and Laucirica, \{Daniel R.\} and Watkins, \{M. Ebru\} and Feske, \{Marsha L.\} and Garcia-Bustillos, \{Jesus R.\} and Chau Vu and Concepcion Cantu and Shelburne, \{Samuel A.\} and Nahuel Fittipaldi and Muthiah Kumaraswami and Shea, \{Patrick R.\} and Flores, \{Anthony R.\} and Beres, \{Stephen B.\} and Maguerite Lovgren and Tyrrell, \{Gregory J.\} and Androulla Efstratiou and Low, \{Donald E.\} and \{Van Beneden\}, \{Chris A.\} and Musser, \{James M.\}",

note = "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.",

year = "2012",

month = jun,

day = "1",

doi = "10.1093/infdis/jir825",

language = "English",

volume = "205",

pages = "1719--1729",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "11",

}

Olsen, RJ, Laucirica, DR, Watkins, ME, Feske, ML, Garcia-Bustillos, JR, Vu, C, Cantu, C, Shelburne, SA, Fittipaldi, N, Kumaraswami, M, Shea, PR, Flores, AR, Beres, SB, Lovgren, M, Tyrrell, GJ, Efstratiou, A, Low, DE, Van Beneden, CA & Musser, JM 2012, 'Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus', Journal of Infectious Diseases, vol. 205, no. 11, pp. 1719-1729. https://doi.org/10.1093/infdis/jir825

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 A.

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 - https://www.scopus.com/pages/publications/84861033764

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 -

Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group a streptococcus

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this