title: Staphylococcus epidermidis Esp degrades specific proteins associated with Staphylococcus aureus biofilm formation and host-pathogen interaction.
abstract: Staphylococcus aureus exhibits a strong capacity to attach to abiotic or biotic surfaces and form biofilms, which lead to chronic infections. We have recently shown that Esp, a serine protease secreted by commensal Staphylococcus epidermidis, disassembles preformed biofilms of S. aureus and inhibits its colonization. Esp was expected to degrade protein determinants of the adhesive and cohesive strength of S. aureus biofilms. The aim of this study was to elucidate the substrate specificity and target proteins of Esp and thereby determine the mechanism by which Esp disassembles S. aureus biofilms. We used a mutant Esp protein (Esp(S235A)) with defective proteolytic activity; this protein did not disassemble the biofilm formed by a clinically isolated methicillin-resistant S. aureus (MRSA) strain, thereby indicating that the proteolytic activity of Esp is essential for biofilm disassembly. Esp degraded specific proteins in the biofilm matrix and cell wall fractions, in contrast to proteinase K, which is frequently used for testing biofilm robustness and showed no preference for proteolysis. Proteomic and immunological analyses showed that Esp degrades at least 75 proteins, including 11 biofilm formation- and colonization-associated proteins, such as the extracellular adherence protein, the extracellular matrix protein-binding protein, fibronectin-binding protein A, and protein A. In addition, Esp selectively degraded several human receptor proteins of S. aureus (e.g., fibronectin, fibrinogen, and vitronectin) that are involved in its colonization or infection. These results suggest that Esp inhibits S. aureus colonization and biofilm formation by degrading specific proteins that are crucial for biofilm construction and host-pathogen interaction.
authors: Department of Bacteriology, The Jikei University School of Medicine, Tokyo, Japan. ssugimoto@jikei.ac.jp
authors: Shinya
authors: S
authors: Sugimoto
authors: Takeo
authors: T
authors: Iwamoto
authors: Koji
authors: K
authors: Takada
authors: Ken-Ichi
authors: K
authors: Okuda
authors: Akiko
authors: A
authors: Tajima
authors: Tadayuki
authors: T
authors: Iwase
authors: Yoshimitsu
authors: Y
authors: Mizunoe
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D001798:Blood Proteins / Q000737:chemistry; D002473:Cell Wall; D005109:Extracellular Matrix / Q000737:chemistry; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D057057:Serine Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride; D013211:Staphylococcus aureus / Q000502:physiology* / Q000648:ultrastructure; D013212:Staphylococcus epidermidis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D001798:Blood Proteins; D008565:Membrane Proteins; D012965:Sodium Chloride; D057057:Serine Proteases