title: Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors.
abstract: Streptococcus pyogenes is an important human pathogen that causes invasive diseases such as necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome. We investigated the function of a major cysteine protease from S. pyogenes that affects the amount of C1-esterase inhibitor (C1-INH) and other complement factors and aimed to elucidate the mechanism involved in occurrence of streptococcal toxic shock syndrome from the aspect of the complement system. First, we revealed that culture supernatant of a given S. pyogenes strain and recombinant SpeB degraded the C1-INH. Then, we determined the N-terminal sequence of the C1-INH fragment degraded by recombinant SpeB. Interestingly, the region containing one of the identified cleavage sites is not present in patients with C1-INH deficiency. Scanning electron microscopy of the speB mutant incubated in human serum showed the abnormal superficial architecture and irregular oval structure. Furthermore, unlike the wild-type strain, that mutant strain showed lower survival capacity than normal as compared with heat-inactivated serum, whereas it had a significantly higher survival rate in serum without the C1-INH than in normal serum. Also, SpeB degraded multiple complement factors and the membrane attack complex. Flow cytometric analyses revealed deposition of C9, one of the components of membrane the attack complex, in greater amounts on the surface of the speB mutant, whereas lower amounts of C9 were bound to the wild-type strain surface. These results suggest that SpeB can interrupt the human complement system via degrading the C1-INH, thus enabling S. pyogenes to evade eradication in a hostile environment.
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Honda-Ogawa
authors.forename: Taiji
authors.initials: T
authors.lastname: Ogawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sumitomo
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakata
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebe
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003186:Complement C9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005098:Exotoxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D050718:Complement C1 Inhibitor Protein; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D005098:Exotoxins; C027951:erythrogenic toxin; D003546:Cysteine Endopeptidases
keywords: C1-Esterase Inhibitor; Complement System; Cysteine Protease; Innate Immunity; Membrane Attack Complex; Protease Inhibitor; SpeB; Streptococcus pyogenes