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.
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.
Miyoshi-Akiyama
Tohru
T
Department of Infectious Diseases, International Medical Center of Japan, Tokyo, Japan. takiyama@ri.imcj.go.jp
Ikebe
Tadayoshi
T
Watanabe
Haruo
H
Uchiyama
Takehiko
T
Kirikae
Teruo
T
Kawamura
Yoshiaki
Y
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D016019:Survival Analysis; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D004269:DNA, Bacterial; D012097:Repressor Proteins; D006820:Hyaluronic Acid