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Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 Group A Streptococcus
Author(s) -
Olsen Randall J,
Laucirica Daniel R,
Watkins Melanie E,
Feske Marsha L,
Garcia-Bustillos Jesus R,
Vu Chau,
Cantu Concepcion,
Shelburne Samuel A,
Fittipaldi Nahuel,
Kumaraswami Muthiah,
Shea Patrick,
Flores Anthony R,
Beres Stephen B,
Lovgren Maguerite,
Tyrrell Gregory J,
Efstratiou Androulla,
Low Donald E,
Van Beneden Chris A,
Musser James M
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1034.3
Subject(s) - virulence , biology , serotype , gene , whole genome sequencing , protease , microbiology and biotechnology , genome , streptococcus , genetics , phenotype , allele , strain (injury) , virology , bacteria , biochemistry , anatomy , enzyme
Whole‐genome sequencing of serotype M3 group A Streptococcus (GAS) strains recovered 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, we sequenced this gene in 1,178 strains collected from different infection types, geographic regions and time periods. The results confirmed our hypothesis by identifying 84 distinct ropB alleles and discovered a significant association between ropB mutations, decreased secreted protease activity of its major regulatory target SpeB, and oropharyngeal infection. Additionally, compared to the parental wild‐type strain, isoallelic strains with ropB polymorphisms were significantly less virulent in mice. 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.