Binding of Streptococcus pneumoniae Endopeptidase O (PepO) to Complement Component C1q Modulates the Complement Attack and Promotes Host Cell Adherence

Agarwal, Vaibhav; Sroka, Magdalena; Fulde, Marcus; Bergmann, Simone; Riesbeck, Kristian; Blom, Anna M.

doi:10.1074/jbc.m113.530212

Cited by 66 publications

(96 citation statements)

References 35 publications

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“…Also, in vivo analysis using a mouse model revealed that S. pneumoniae PepO induces a strong innate immune response via the Toll-like receptor (TLR) 2 and TLR4 signaling pathways (26). Furthermore, secretory PepO of S. pneumoniae has an affinity to human C1q, thereby inhibiting C3b opsonization (16). On the other hand, surface-associated PepO contributes to bacterial adherence to host cells via its interaction with C1q.…”

Section: Discussionmentioning

confidence: 99%

“…pyogenes PepO Interacts with Human Complement Factor C1q-S. pneumoniae PepO has been shown to bind to human complement factor C1q, which leads to bacterial evasion from complement immunity via a classical pathway (16). Thus, we examined the direct interaction between S. pyogenes PepO and human C1q by SPR analysis at pH 7.4 ( Fig.…”

Section: S Pyogenes Endopeptidase Pepo Is Conserved and Expressed Inmentioning

confidence: 99%

“…Complement activity in infected tissues was analyzed using a CH 50 complement activity measuring kit (Denka Seiken Co., Ltd., Tokyo, Japan), as previously described (16,41). Briefly, PBS was injected into the flank on one side and the WT (n ϭ 7 mice) or ⌬pepO (n ϭ 6 mice) strain into the flank on the other side of individual mice.…”

Section: Construction Of S Pyogenes Mutant Strain and Recombinantmentioning

confidence: 99%

“…Direct Binding Assay-Direct binding assays were performed as previously described (16). Briefly, 96-well plates (Sumitomo Bakelite Co., Ltd., Tokyo, Japan) were coated with 500 ng of rPepO and human IgG (IgG) in 0.1 M bicarbonate buffer (pH 9.8) overnight at 4°C.…”

Section: Construction Of S Pyogenes Mutant Strain and Recombinantmentioning

confidence: 99%

“…Recently, endopeptidase O (PepO) secreted from Streptococcus pneumoniae has been shown to bind to C1q and affect opsonophagocytosis (16). S. pyogenes possesses a homologue with a 68% homology to S. pneumoniae PepO on the amino acid level.…”

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confidence: 99%

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

Honda-Ogawa

Sumitomo

Mori

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillStreptococcus 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 (⌬pepO) 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 ⌬pepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with ⌬pepO. 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.The human pathogen Streptococcus pyogenes is a ␤-hemolytic Gram-positive bacterium that causes a wide variety of diseases in various anatomical sites. Superficial infection of S. pyogenes generally leads to local suppurative lesions, such as seen in pharyngitis and impetigo cases. Such mucosal and skin infections are occasionally followed by onset of immune sequelae, including acute rheumatic fever and acute glomerulonephritis. Furthermore, S. pyogenes infection can also cause invasive diseases, such as necrotizing fasciitis, cellulitis, bacteremia, and streptococcal toxic shock syndrome (STSS), 2 with a high mortality rate, which has been a serious problem throughout the world (1-3).Host possesses various immune systems such as the complement system, one of the most important components of innate immunity, that contributes to host defense against pathogens, especially in the early stage of infection (4). Recognition of an invading pathogen is the trigger for complement pathway activation, and then each complement factor is activated in a sequential manner with precise control (5). Together with opsonization, complement-mediated direct killing of pathogens is attributable to formation of the membrane attack complex (MAC), which consists of late complement factors and induces bacteriolysis by pore formati...

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Section: Discussionmentioning

confidence: 99%

Section: S Pyogenes Endopeptidase Pepo Is Conserved and Expressed Inmentioning

confidence: 99%

Section: Construction Of S Pyogenes Mutant Strain and Recombinantmentioning

confidence: 99%

Section: Construction Of S Pyogenes Mutant Strain and Recombinantmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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

Honda-Ogawa

Sumitomo

Mori

et al. 2017

Journal of Biological Chemistry

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Protein Moonlighting and Infectious Disease

2016

Protein Moonlighting in Biology and Medicine

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Streptococcus endopeptidases promote HPV infection in vitro

et al. 2018

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Both cervical and throat cancers are associated with human papillomavirus (HPV). HPV infection requires cleavage of the minor capsid protein L2 by furin. While furin is present in the vaginal epithelium, it is absent in oral epithelial basal cells where HPV infection occurs. The objective of this study was to investigate whether common oral bacteria express furin‐like peptidases. By screening strains representing 12 oral Streptococcus and Enterococcus species, we identified that eight Streptococcus strains displayed high levels of furin‐like peptidase activity, with S. gordonii V2016 the highest. We constructed null mutations for 14 genes encoding putative endopeptidases in S. gordonii V2016. Results showed that three endopeptidases, PepO, PulO, and SepM, had furin‐like activities. All three mutants showed decreased natural transformation by chromosomal DNA, while the pepO mutant also showed reduced transformation by plasmid DNA, indicating involvement of these endopeptidases in competence development. The purified S. gordonii PepO protein promoted infection of epithelial 293TT cells in vitro by HPV16 pseudovirus. In conclusion, oral bacteria might promote HPV infection and contribute to HPV tissue tropism and subsequent carcinogenesis in the oral cavity and throat by providing furin‐like endopeptidases.

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Binding of Streptococcus pneumoniae Endopeptidase O (PepO) to Complement Component C1q Modulates the Complement Attack and Promotes Host Cell Adherence

Cited by 66 publications

References 35 publications

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

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

Protein Moonlighting and Infectious Disease

Streptococcus endopeptidases promote HPV infection in vitro

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