Use of DNA arrays to identify a mutation in the negative regulator, csrR, responsible for the high virulence of a naturally occurring type M3 group A streptococcus clinical isolate

Tohru Miyoshi-Akiyama; Tadayoshi Ikebe; Haruo Watanabe; Takehiko Uchiyama; Teruo Kirikae; Yoshiaki Kawamura

doi:10.1086/504263

Use of DNA arrays to identify a mutation in the negative regulator, csrR, responsible for the high virulence of a naturally occurring type M3 group A streptococcus clinical isolate

J Infect Dis. 2006 Jun 15;193(12):1677-84. doi: 10.1086/504263. Epub 2006 May 10.

Authors

Tohru Miyoshi-Akiyama¹, Tadayoshi Ikebe, Haruo Watanabe, Takehiko Uchiyama, Teruo Kirikae, Yoshiaki Kawamura

Affiliation

¹ Department of Infectious Diseases, International Medical Center of Japan, Tokyo, Japan. takiyama@ri.imcj.go.jp

PMID: 16703511
DOI: 10.1086/504263

Abstract

We previously reported that type M3 group A streptococcus (GAS) showed a wide range of 50% lethal dose values in mice. Analysis using DNA arrays indicated that the most virulent strain, M3-f, expressed significantly higher levels of the products of several virulence genes than did the other M3 isolates. Sequencing of the csrS, csrR, luxS, and rgg genes in the isolates showed that the M-3f csrR gene contained a specific point mutation. Disruption of wild-type (wt) csrR in an M3 strain increased its virulence and the expression of hyaluronic acid, whereas complementation with wt but not type M3-f csrR attenuated these changes. Expression experiments showed that type M3-f CsrR counteracted the effects of wt CsrR. Although wt CsrR bound to the hasA promoter region, type M3-f CsrR did not. Thus, the high virulence of the type M3-f strain is associated with the decreased binding of type M3-f CsrR to its target sequences.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Bacterial Proteins / biosynthesis
Bacterial Proteins / genetics*
Bacterial Proteins / metabolism
DNA, Bacterial / chemistry
DNA, Bacterial / genetics
Disease Models, Animal
Electrophoretic Mobility Shift Assay
Female
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation, Bacterial*
Genetic Complementation Test
Hyaluronic Acid / biosynthesis
Lethal Dose 50
Mice
Molecular Sequence Data
Mutagenesis, Insertional
Oligonucleotide Array Sequence Analysis
Point Mutation*
Promoter Regions, Genetic
Protein Binding
Repressor Proteins / biosynthesis
Repressor Proteins / genetics*
Repressor Proteins / metabolism
Sequence Analysis, DNA
Streptococcal Infections / microbiology
Streptococcus pyogenes / genetics
Streptococcus pyogenes / isolation & purification
Streptococcus pyogenes / pathogenicity*
Survival Analysis
Virulence / genetics

Substances

Bacterial Proteins
CsrR protein, Streptococcus pyogenes
DNA, Bacterial
Repressor Proteins
Hyaluronic Acid