Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice.
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 emm1 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 emm1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28 SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined during subcutaneous infection of mice. The majority of both invasive and pharyngeal emm1 SpeBA+ isolates and two of three emm12 isolates, but not emm3 and emm28 isolates, were found to acquire SpeBA- variants during skin infection in mice. All analyzed SpeBA- variants of emm1 and emm12 GAS from the mouse infection acquired covRS mutations and produced more platelet-activating factor acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm1 GAS isolates and emm12 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.
Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59718, United States of America.
Wenchao
W
Feng
Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59718, United States of America.
Mengyao
M
Liu
Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59718, United States of America.
Daniel G
DG
Chen
Harborview Medical Center Clinical Microbiology Laboratory and University of Washington School of Medicine, Seattle, Washington, United States of America.
Rossana
R
Yiu
Harborview Medical Center Clinical Microbiology Laboratory and University of Washington School of Medicine, Seattle, Washington, United States of America.
Ferric C
FC
Fang
Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59718, United States of America.
Benfang
B
Lei
D000483:Alleles; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D005838:Genotype; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D010614:Pharynx / Q000382:microbiology* / Q000473:pathology; D010641:Phenotype; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000382:microbiology / Q000473:pathology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein