Streptococcus pyogenesEndopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q.
Streptococcus pyogenessecretes various virulence factors for evasion from complement-mediated bacteriolysis. However, full understanding of the molecules possessed by this organism that interact with complement C1q, an initiator of the classical complement pathway, remains elusive. In this study, we identified an endopeptidase ofS. pyogenes, PepO, as an interacting molecule, and investigated its effects on complement immunity and pathogenesis. Enzyme-linked immunosorbent assay and surface plasmon resonance analysis findings revealed thatS. pyogenesrecombinant PepO bound to human C1q in a concentration-dependent manner under physiological conditions. Sites of inflammation are known to have decreased pH levels, thus the effects of PepO on bacterial evasion from complement immunity was analyzed in a low pH condition. Notably, under low pH conditions, PepO exhibited a higher affinity for C1q as compared with IgG, and PepO inhibited the binding of IgG to C1q. In addition,pepOdeletion renderedS. pyogenesmore susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of thepepOmutant strain (ΔpepO) showed damaged irregular surfaces as compared with the wild-type strain (WT). WT-infected tissues exhibited greater severity and lower complement activity as compared with those infected by ΔpepOin a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with ΔpepO.Our results suggest that interaction ofS. pyogenesPepO with C1q interferes with the complement pathway, which enablesS. pyogenesto evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites.
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.
Mariko
M
Honda-Ogawa
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.
Tomoko
T
Sumitomo
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.|Division of Special Care Dentistry, Osaka University Dental Hospital, and.
Yasushi
Y
Mori
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.
Dalia Talat
DT
Hamd
Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
Taiji
T
Ogawa
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.
Masaya
M
Yamaguchi
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.
Masanobu
M
Nakata
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, kawabata@dent.osaka-u.ac.jp.
Shigetada
S
Kawabata
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D001433:Bacteriolysis / Q000276:immunology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D010450:Endopeptidases / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology* / Q000378:metabolism; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity
D001426:Bacterial Proteins; D015922:Complement C1q; D010450:Endopeptidases; C445310:PepO protein, Streptococcus pneumoniae
C1Q complex (C1QA); Streptococcus pyogenes (S. pyogenes); complement system; innate immunity; peptidase