Open AccessContemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice
Author(s) -
Wenchao Feng,
Mengyao Liu,
Daniel G. Chen,
Rossana Yiu,
Ferric C. Fang,
Benfang Lei
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0162742
Subject(s) - biology , virulence , mutant , streptococcus , streptococcus pyogenes , microbiology and biotechnology , genotype , group a , gene , genetics , bacteria , staphylococcus aureus , medicine
Group A Streptococcus (GAS) causes diverse infections ranging from common pharyngitis to rare severe invasive infections. Invasive GAS isolates can have natural mutations in the virulence regulator CovRS, which result in enhanced expression of multiple virulence genes, suppressed the expression of the protease SpeB, and increased virulence. It is believed that CovRS mutations arise during human infections with GAS carrying wild-type CovRS and are not transmissible. CovRS mutants of invasive GAS of the emm 1 genotype arise readily during experimental infection in mice. It is possible that invasive GAS arises from pharyngeal GAS through rare genetic mutations that confer the capacity of mutated GAS to acquire covRS mutations during infection. The objective of this study was to determine whether contemporary pharyngeal emm 1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm 1 GAS and whether emm 3, emm 12, and emm 28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm 1 and invasive emm 3, emm 12, and emm 28 SpeB A+ isolates to acquire variants with the SpeB A- phenotype was determined during subcutaneous infection of mice. The majority of both invasive and pharyngeal emm 1 SpeB A+ isolates and two of three emm 12 isolates, but not emm 3 and emm 28 isolates, were found to acquire SpeB A- variants during skin infection in mice. All analyzed SpeB A- variants of emm 1 and emm 12 GAS from the mouse infection acquired covRS mutations and produced more platelet-activating factor acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm 1 GAS isolates and emm 12 GAS have a similar capacity to acquire covRS mutations in vivo . The rarity of severe invasive infections caused by GAS does not appear to be attributable to a reduced ability of pharyngeal isolates to acquire CovRS mutations.