title: Staphylococcal proteases aid in evasion of the human complement system.
abstract: Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inhibitors. The effect of extracellular proteases from this bacterium on complement, however, has been the subject of limited investigation, except for a recent report regarding cleavage of the C3 component by aureolysin (Aur). We demonstrate here that four major extracellular proteases of S. aureus are potent complement inhibitors. Incubation of human serum with the cysteine proteases staphopain A and staphopain B, the serine protease V8 and the metalloproteinase Aur resulted in a drastic decrease in the hemolytic activity of serum, whereas two staphylococcal serine proteases D and E, had no effect. These four proteases were found to inhibit all pathways of complement due to the efficient degradation of several crucial components. Furthermore, S. aureus mutants lacking proteolytic enzymes were found to be more efficiently killed in human blood. Taken together, the major proteases of S. aureus appear to be important for pathogen-mediated evasion of the human complement system.
authors.affiliation: Section of Medical Protein Chemistry, Department of Laboratory Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Jusko
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kantyka
authors.forename: Ewa
authors.initials: E
authors.lastname: Bielecka
authors.forename: Halie K
authors.initials: HK
authors.lastname: Miller
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kalinska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dubin
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D057131:Immune Evasion; D008666:Metalloendopeptidases / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D003165:Complement System Proteins; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase; D003546:Cysteine Endopeptidases; C501295:staphopain A protein, Staphylococcus aureus; C479137:staphopain B protein, Staphylococcus aureus; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus