title: Novel DNA binding protein SarZ contributes to virulence in Staphylococcus aureus.
abstract: We previously reported that the cvfA gene is a virulence regulatory gene in Staphylococcus aureus. Here, we identified a novel gene named sarZ that acts as a multicopy suppressor of decreased haemolysin production in the cvfA deletion mutant. The amount of sarZ transcripts was decreased in the cvfA mutant. The sarZ-deletion mutant produced less haemolysin and attenuated virulence in a silkworm-infection model and a mouse-infection model. The amino acid sequence of the sarZ gene product had 19% identity with the transcription factor MarR in Escherichia coli, and the internal region contained a winged helix-turn-helix motif (wHTH), a known DNA binding domain. Purified recombinant SarZ protein had binding affinity for the promoter region of the hla gene that encodes alpha-haemolysin. SarZ mutant proteins with an amino acid substitution in the N-terminal region or in the wHTH motif had significantly decreased DNA binding. The mutated sarZ genes encoding SarZ mutant proteins with a low affinity for DNA did not complement the decreased haemolysin production or the attenuated killing ability against silkworms in the sarZ mutant. These results suggest that the DNA binding activity of the SarZ protein is required for virulence in S. aureus.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 3-1, 7-Chome, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kaito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morishita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D012831:Bombyx / Q000382:microbiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D019077:Helix-Turn-Helix Motifs; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D006460:Hemolysin Proteins; D011993:Recombinant Fusion Proteins; C021091:staphylococcal alpha-toxin; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus