TY - JOUR
T1 - Intergenic variable-number tandem-repeat polymorphism upstream of rocA alters toxin production and enhances virulence in Streptococcus pyogenes
AU - Zhu, Luchang
AU - Olsen, Randall J.
AU - Horstmann, Nicola
AU - Shelburne, Samuel A.
AU - Fan, Jia
AU - Hu, Tony
AU - Musser, James M.
N1 - Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016/5/2
Y1 - 2016/5/2
N2 - Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes. The nature of the polymorphism is a one-unit deletion in a three-tandemrepeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes.
AB - Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes. The nature of the polymorphism is a one-unit deletion in a three-tandemrepeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes.
UR - http://www.scopus.com/inward/record.url?scp=84976883195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84976883195&partnerID=8YFLogxK
U2 - 10.1128/IAI.00258-16
DO - 10.1128/IAI.00258-16
M3 - Article
C2 - 27141081
SN - 0019-9567
VL - 84
SP - 2086
EP - 2093
JO - Infection and Immunity
JF - Infection and Immunity
IS - 7
ER -