RRC ID 11322
著者 Nagata M, Kaito C, Sekimizu K.
タイトル Phosphodiesterase activity of CvfA is required for virulence in Staphylococcus aureus.
ジャーナル J Biol Chem
Abstract We previously identified the cvfA gene (SA1129) as a novel virulence regulator in Staphylococcus aureus using the silkworm infection model. The cvfA gene, which is conserved among various pathogenic bacteria, contributes to the expression of the agr locus, a global virulence regulator that controls the expression of genes encoding various exoproteins, such as hemolysin. CvfA protein has a transmembrane domain, an RNA binding domain (KH domain), and a metal-dependent phosphohydrolase domain (HD domain). We report here the purification of recombinant CvfA protein from a membrane fraction of Escherichia coli by measuring its phosphodiesterase activity. Purified CvfA protein hydrolyzed the phosphodiester linkage of 2',3'-cyclic AMP, 2',3'-cyclic GMP, and 2',3'-cyclic phosphate at the 3'-terminal of RNA in the presence of Mn(2+). CvfA mutant proteins with amino acid substitutions in the HD domain had significantly decreased phosphodiesterase activity. Furthermore, mutated cvfA genes encoding proteins with low phosphodiesterase activity did not complement the decreased hemolysin production or the attenuated killing ability against silkworms in the cvfA deletion mutant. These results suggest that the phosphodiesterase activity of CvfA protein is required for virulence in S. aureus.
巻・号 283(4)
ページ 2176-84
公開日 2008-1-25
DOI 10.1074/jbc.M705309200
PII S0021-9258(20)77651-9
PMID 17951247
MeSH Animals Bacterial Proteins / genetics Bacterial Proteins / metabolism* Bombyx / enzymology Bombyx / genetics Bombyx / microbiology Cyclic AMP / metabolism Cyclic GMP / metabolism Disease Models, Animal Gene Expression Regulation, Bacterial / physiology Hemolysin Proteins / biosynthesis Hemolysin Proteins / genetics Humans Hydrolysis Manganese Membrane Proteins / genetics Membrane Proteins / metabolism* Metalloproteins / genetics Metalloproteins / metabolism* Mutation Phosphates / metabolism Phosphoric Diester Hydrolases / genetics Phosphoric Diester Hydrolases / metabolism* Protein Structure, Tertiary / physiology RNA / metabolism RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Recombinant Proteins / genetics Recombinant Proteins / metabolism Staphylococcal Infections / enzymology Staphylococcal Infections / genetics Staphylococcus aureus / enzymology* Staphylococcus aureus / genetics Staphylococcus aureus / pathogenicity*
IF 4.238
引用数 48
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
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