Interpain A, a Cysteine Proteinase from Prevotella intermedia, Inhibits Complement by Degrading Complement Factor C3

被引:90
作者
Potempa, Michal [1 ,2 ]
Potempa, Jan [2 ,3 ]
Kantyka, Tomasz [2 ]
Nguyen, Ky-Anh [4 ]
Wawrzonek, Katarzyna [2 ]
Manandhar, Surya P. [4 ]
Popadiak, Katarzyna [1 ,2 ]
Riesbeck, Kristian [5 ]
Eick, Sigrun [6 ]
Blom, Anna M. [1 ]
机构
[1] Lund Univ, Malmo Univ Hosp, Sect Med Prot Chem, Dept Lab Med, Malmo, Sweden
[2] Jagiellonian Univ, Dept Microbiol, Krakow, Poland
[3] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA
[4] Inst Dent Res, Westmead Millennium Inst, Sydney, NSW, Australia
[5] Lund Univ, Malmo Univ Hosp, Sect Med Microbiol, Dept Lab Med, Malmo, Sweden
[6] Univ Hosp Jena, Dept Med Microbiol, Jena, Germany
基金
美国国家卫生研究院; 瑞典研究理事会;
关键词
POLYMERASE-CHAIN-REACTION; PORPHYROMONAS-GINGIVALIS; BACTEROIDES-GINGIVALIS; PERIODONTAL PATHOGENS; BACTERICIDAL ACTIVITY; C4B-BINDING PROTEIN; COMPONENTS C3; HUMAN-SERUM; DEGRADATION; ACTIVATION;
D O I
10.1371/journal.ppat.1000316
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A) resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3-the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.
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页数:14
相关论文
共 48 条
[1]   Polymerase chain reaction detection of 8 putative periodontal pathogens in subgingival plaque of gingivitis and advanced periodontitis lesions [J].
Ashimoto, A ;
Chen, C ;
Bakker, I ;
Slots, J .
ORAL MICROBIOLOGY AND IMMUNOLOGY, 1996, 11 (04) :266-273
[2]   COMPLEMENT FACTORS IN GINGIVAL CREVICE MATERIAL FROM HEALTHY AND INFLAMED GINGIVA IN HUMANS [J].
ATTSTROM, R ;
LAUREL, AB ;
LAHSSON, U ;
SJOHOLM, A .
JOURNAL OF PERIODONTAL RESEARCH, 1975, 10 (01) :19-27
[3]  
Aurer A, 2005, COLLEGIUM ANTROPOL, V29, P435
[4]   Complement inhibitor C4b-binding protein -: friend or foe in the innate immune system? [J].
Blom, AM ;
Villoutreix, BO ;
Dahlbäck, B .
MOLECULAR IMMUNOLOGY, 2004, 40 (18) :1333-1346
[5]  
CUTLER CW, 1993, J IMMUNOL, V151, P7016
[6]   Microbiology of periodontal disease in children and young adults [J].
Darby, I ;
Curtis, M .
PERIODONTOLOGY 2000, 2001, 26 :33-53
[7]   Cleavage of CD14 and LBP by a protease from Prevotella intermedia [J].
Deschner, J ;
Singhal, A ;
Long, P ;
Liu, CC ;
Piesco, N ;
Agarwal, S .
ARCHIVES OF MICROBIOLOGY, 2003, 179 (06) :430-436
[8]   Characterization of protease activities in Capnocytophaga spp., Porphyromonas gingivalis, Prevotella spp., Treponema denticola and Actinobacillus actinomycetemcomitans [J].
Gazi, MI ;
Cox, SW ;
Clark, DT ;
Eley, BM .
ORAL MICROBIOLOGY AND IMMUNOLOGY, 1997, 12 (04) :240-248
[9]  
Gmür R, 2002, MICROBIOL-SGM, V148, P1379, DOI 10.1099/00221287-148-5-1379
[10]   Degradation of host protease inhibitors and activation of plasminogen by proteolytic enzymes from Porphyromonas gingivalis and Treponema denticola [J].
Grenier, D .
MICROBIOLOGY-UK, 1996, 142 :955-961