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J Biol Chem. 2017 Mar 10;292(10):4244-4254. doi: 10.1074/jbc.M116.749275. Epub 2017 Jan 30.

Streptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q.

Author information

1
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry.
2
Division of Special Care Dentistry, Osaka University Dental Hospital, and.
3
Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
4
From the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, kawabata@dent.osaka-u.ac.jp.

Abstract

Streptococcus pyogenes secretes 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 of S. 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 that S. pyogenes recombinant 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, pepO deletion rendered S. pyogenes more susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of the pepO mutant 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 ΔpepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with ΔpepO. Our results suggest that interaction of S. pyogenes PepO with C1q interferes with the complement pathway, which enables S. pyogenes to evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites.

KEYWORDS:

C1Q complex (C1QA); Streptococcus pyogenes (S. pyogenes); complement system; innate immunity; peptidase

PMID:
28154192
PMCID:
PMC5354489
DOI:
10.1074/jbc.M116.749275
[Indexed for MEDLINE]
Free PMC Article

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