Binding of Complement Inhibitor C4b-Binding Protein Contributes to Serum Resistance of <i>Porphyromonas gingivalis</i>

Potempa, Michał; Potempa, Jan; Okrój, Marcin; Popadiak, Katarzyna; Eick, Sigrun; Nguyen, Ky-Anh; Riesbeck, Kristian; Blom, Anna M.

doi:10.4049/jimmunol.181.8.5537

Cited by 76 publications

(74 citation statements)

References 51 publications

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“…An enhanced bactericidal activity of taurolidine in the presence of serum as described before [34] was not always found. This might be associated with a resistance of many periodontopathogens against killing by complement [35,36]. In killing assays, both the potential inhibiting effect of serum proteins and the complement activity are combined with the efficacy of the antimicrobials.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of taurolidine against periodontopathic species—an in vitro study

et al. 2011

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The antimicrobial effect of taurolidine was tested against periodontopathic species in comparison to chlorhexidine digluconate in the presence or absence of serum. Minimal inhibitory concentrations (MIC), microbiocidal concentrations (MBC), as well as killing were determined against 32 different microbial strains including 3 Porphyromonas gingivalis, 3 Aggregatibacter actinomycetemcomitans, and 15 potentially superinfecting species with and without 25% v/v human serum. The MIC 50 of taurolidine against the tested microbial strains was 0.025% and the MIC 90 0.05%. The respective values for the MBCs were 0.05% and 0.1%. Addition of 25% serum (heat-inactivated) did not change the MIC and MBC values of taurolidine. In contrast, MICs and MBCs of chlorhexidine (CHX) increased by two steps after addition of serum. Taurolidine killed microorganisms in a concentration and timedependent manner, the killing rate of 1.6% taurolidine was 99.08%±2.27% in mean after 2 h. Again, killing activity of taurolidine was not affected if serum was added, whereas addition of inactivated serum clearly reduced the killing rate of all selected bacterial strains by CHX. Therefore, taurolidine possesses antimicrobial properties which are not reduced in the presence of serum as a main component in gingival crevicular fluid and wound fluid. Taurolidine may have potential as an antimicrobial agent in non-surgical and surgical periodontal treatment.

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Section: Discussionmentioning

confidence: 99%

Efficacy of taurolidine against periodontopathic species—an in vitro study

et al. 2011

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“…Inhibition of C3b deposition by recruiting the complement-controlling protein factor H or C4BP contributes to serum resistance (30,32,33). Factor H inhibits the alternative pathway in complement activation, while C4BP inhibits the classical and lectin pathways.…”

Section: Resultsmentioning

confidence: 99%

“…Bacterial components such as lipopolysaccharides (LPS), peptidoglycan, and lipoproteins can induce complement activation. However, many bacteria, including periodontal pathogens, are resistant to human serum (16,(30)(31)(32)(33). Coaggregation between different bacteria plays a key role in the colonization of the gingival crevice and the organization of biofilm formation by periodontal pathogens.…”

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confidence: 99%

The Surface Layer of Tannerella forsythia Contributes to Serum Resistance and Oral Bacterial Coaggregation

et al. 2013

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e Tannerella forsythia is an anaerobic, Gram-negative bacterium involved in the so-called "red complex," which is associated with severe and chronic periodontitis. The surface layer (S-layer) of T. forsythia is composed of cell surface glycoproteins, such as TfsA and TfsB, and is known to play a role in adhesion/invasion and suppression of proinflammatory cytokine expression. Here we investigated the association of this S-layer with serum resistance and coaggregation with other oral bacteria. The growth of the S-layer-deficient mutant in a bacterial medium containing more than 20% non-heat-inactivated calf serum (CS) or more than 40% non-heat-inactivated human serum was significantly suppressed relative to that of the wild type (WT). Next, we used confocal microscopy to perform quantitative analysis on the effect of serum. The survival ratio of the mutant exposed to 100% non-heat-inactivated CS (76% survival) was significantly lower than that of the WT (97% survival). Furthermore, significant C3b deposition was observed in the mutant but not in the WT. In a coaggregation assay, the mutant showed reduced coaggregation with Streptococcus sanguinis, Streptococcus salivarius, and Porphyromonas gingivalis but strong coaggregation with Fusobacterium nucleatum. These results indicated that the S-layer of T. forsythia plays multiple roles in virulence and may be associated with periodontitis.

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“…Pathogens such as S. pyogenes (62) and N. gonorrheae (18) interact with CCP1, N. meningitidis (17) binds CCP2 and CCP3, whereas E. coli K1 targets CCP3 and CCP8 (16). P. gingivalis interacts with CCP1 and CCP6 and CCP7 (25), whereas B. pertussis (63) and the yeast and the hyphae form of C. albicans (24) interact mainly with CCP1 and CCP2. Recently, C. albicans Pra1 protein has been shown to interact with CCP4, CCP7, and CCP8 of C4BP (23).…”

Section: Figurementioning

confidence: 99%

“…A common mechanism is the interaction with complement inhibitors such as factor H (FH) or C4BP, thereby facilitating immune evasion. Pathogenic microorganisms including Streptococcus pyogenes (14,15), Escherichia coli K1 (16), Neisseria meningitidis (17), Neisseria gonorrheae (18), the Lyme disease spirochetes Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii (19), Bordetella pertussis (20), Moraxella catarrhalis (21), Haemophilus influenzae (22), Candida albicans (23,24) and Porphyromonas gingivalis (25) have been reported to bind C4BP. It has been demonstrated that pneumococci bind complement inhibitors C4BP and FH via PspC protein (7,26,27), with the binding of C4BP being PspC allele dependent.…”

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confidence: 99%

Enolase ofStreptococcus pneumoniaeBinds Human Complement Inhibitor C4b-Binding Protein and Contributes to Complement Evasion

Agarwal

Hammerschmidt

Malm

et al. 2012

The Journal of Immunology

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Streptococcus pneumoniae (pneumococcus) is a pathogen that causes severe local and life-threatening invasive diseases, which are associated with high mortality rates. Pneumococci have evolved several strategies to evade the host immune system, including complement to disseminate and to survive in various host niches. Thus, pneumococci bind complement inhibitors such as C4b-binding protein (C4BP) and factor H via pneumococcal surface protein C, thereby inhibiting the classical and alternative complement pathways. In this study, we identified the pneumococcal glycolytic enzyme enolase, a nonclassical cell surface and plasminogen-binding protein, as an additional pneumococcal C4BP-binding protein. Furthermore, we demonstrated that human, but not mouse, C4BP bound pneumococci. Recombinant enolase bound in a dose-dependent manner C4BP purified from plasma, and the interaction was reduced by increasing ionic strength. Enolase recruited C4BP and plasminogen, but not factor H, from human serum. Moreover, C4BP and plasminogen bound to different domains of enolase as they did not compete for the interaction with enolase. In direct binding assays with recombinant C4BP mutants lacking individual domains, two binding sites for enolase were identified on the complement control protein (CCP) domain 1/CCP2 and CCP8 of the C4BP α-chains. C4BP bound to the enolase retained its cofactor activity as determined by C4b degradation. Furthermore, in the presence of exogenously added enolase, an increased C4BP binding to and subsequently decreased C3b deposition on pneumococci was observed. Taken together, pneumococci specifically interact with human C4BP via enolase, which represents an additional mechanism of human complement control by this versatile pathogen.

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Binding of Complement Inhibitor C4b-Binding Protein Contributes to Serum Resistance of Porphyromonas gingivalis

Cited by 76 publications

References 51 publications

Efficacy of taurolidine against periodontopathic species—an in vitro study

Efficacy of taurolidine against periodontopathic species—an in vitro study

The Surface Layer of Tannerella forsythia Contributes to Serum Resistance and Oral Bacterial Coaggregation

Enolase ofStreptococcus pneumoniaeBinds Human Complement Inhibitor C4b-Binding Protein and Contributes to Complement Evasion

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