The staphylococcal elastin-binding protein regulates zinc-dependent growth/biofilm formation.
Staphylococcus aureus is one of the most important human pathogens because it is a common cause of nosocomial infections. The elastin-binding protein of Staphylococcus aureus (EbpS) is an adhesin that is responsible for attachment to host cells via its binding to elastin. Despite its relatively weak contribution to adhesion, the ebpS gene is highly conserved among S. aureus isolates, suggesting that EbpS may have other crucial functions. Here, we found that EbpS binds Zn(2+) with its N-terminal region, which leads to local conformational changes that result in the assembly of the EbpS protein. The growth rate of the EbpS-deficient strain was considerably decreased. Zn(2+) chelation decreased the growth rate of the wild-type strain but did not alter that of the EbpS-deficient strain. Furthermore, biofilm formation by the EbpS-deficient strain was abnormally enhanced in the Zn(2+) concentration-dependent manner. All the results suggest that ebpS deficiency led to a zinc concentration-dependent inability to modulate the growth/biofilm maturation phase appropriately. Given the high conservation of ebpS and that appropriate regulation of biofilm formation is thought to be essential for effective staphylococcal infection, inhibition of EbpS binding to Zn(2+) could lead to the development of novel therapeutic strategies for controlling S. aureus infections.
Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Makoto
M
Nakakido
Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-
Chihiro
C
Aikawa
Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan ichiro-n.bac@tmd.ac.jp.
Ichiro
I
Nakagawa
Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; Division of Bacteriology, International Research Center for infectious Diseases, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-
Kouhei
K
Tsumoto
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018441:Biofilms / Q000254:growth & development*; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D004549:Elastin / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053838:Scattering, Small Angle; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin; D015032:Zinc
Staphylococcus aureus; biofilm; elastin-binding protein; intrinsically disordered protein; zinc