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 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

Research output: Contribution to journalArticle

23 Scopus citations

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 languageEnglish (US)
Pages (from-to)1719-1729
Number of pages11
JournalJournal of Infectious Diseases
Volume205
Issue number11
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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