Susceptibility of periodontopathogenic and cariogenic bacteria to defensins and potential therapeutic use of defensins in oral diseases

Current Pharmaceutical Design

Volumn 13, Issue 30, 2007, Pages 3084-3095

  Komatsuzawa, Hitoshi ^a   Ouhara, Kazuhisa ^a   Kawai, Toshihisa ^b   Yamada, Sakuo ^c   Fujiwara, Tamaki ^a   Shiba, Hideki ^a   Kurihara, Hidemi ^a   Taubman, Martin A ^b   Sugai, Motoyuki ^a  

^a HIROSHIMA UNIVERSITY   (Japan)

^b FORSYTH INSTITUTE   (United States)

^c KAWASAKI MEDICAL SCHOOL   (Japan)

Author keywords

Antimicrobial peptides; Caries; Oral bacteria; Periodontitis

Indexed keywords

ALPHA DEFENSIN; ANTIBIOTIC AGENT; BETA DEFENSIN; CALGRANULIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; DEFENSIN; HISTATIN; ISEGANAN; POLYPEPTIDE ANTIBIOTIC AGENT; PROTEIN DERIVATIVE;

BACTERIAL COLONIZATION; BACTERIAL GROWTH; BACTERIAL SURVIVAL; CLINICAL TRIAL; DEFENSE MECHANISM; DENTAL CARIES; DISEASE COURSE; DISEASE PREDISPOSITION; DRUG SYNTHESIS; GINGIVA; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HUMAN; INNATE IMMUNITY; MOUTH DISEASE; MOUTH FLORA; MOUTH MUCOSA; MUCOSA INFLAMMATION; PERIODONTITIS; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SALIVARY GLAND; TONGUE;

ANTI-INFECTIVE AGENTS; ANTIMICROBIAL CATIONIC PEPTIDES; BACTERIA; BACTERIAL PHYSIOLOGY; DEFENSINS; DENTAL CARIES; HUMANS; PERIODONTITIS;

EID: 36349034041     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161207782110426     Document Type: Review

References (186)

1. Hamada S, Slade HD. Biology, Immunology, and carigenecity of Streptococcus mutans. Microbiol Rev 1980; 44: 331-84.
2. Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev 1986; 50: 353-80.
3. van Houte J. Role of micro-organisms in caries etiology. J Dent Res 1994; 73: 672-81.
4. Norskov-Lauritsen N, Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int J Syst Evol Microbiol 2006; 56: 2135-46.
5. Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: Diagnosis and treatment: Clin Microbiol Rev 2001; 14(4): 727-52.
6. Loesche WJ, Syed SA, Schmidt E, Morrison EC. Bacterial profiles of subgingival plaques in periodontitis. J Periodontol 1985; 56: 447-56
7. Moore WEC, Moore LVH. The bacteria of periodontal disease. Periodontol 2000 1994; 5: 66-77.
8. Slots J. Subgingival microflora and periodontal disease. J Clin Periodontol 1979; 6: 351-82.
9. Tanner A, Maiden MF, Macuch PJ, Murray LL, Kent JRL. Microbiota of health, gingivitis, and initial periodontitis. J Clin Periodontol 1998; 25: 85-98.
10. Taubman MA, Valverde P, Han X, Kawai T. Immune response: The key to bone resorption in periodontal disease. J Periodontol 2005 76: 2033-41.
11. Beck JD, Garcia RI, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol 1996; 67: 1123-37
12. Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev 2000; 13: 547-58.
13. Limeback H. The relationship between oral Health and systemic infections among elderly residents of chronic care facilities. Gerodontology 1988; 7: 131-7.
14. Loesche WJ, Lopatin DE. Interactions between periodontal disease, medical diseases and immunity in the older individuals. Periodontol 2000 1998; 16: 80-105.
15. Mattila KJ, Valtonen VV, Nicminen M, Huttunen JK. Dental infection and the risk of new coronary events: Prospective study of patients with documented coronary artery disease. Clin Infect Dis 1995; 20: 588-92
16. Page RC. The pathobiology of periodontal diseases may affect systemic diseases: Inversion of a paradigm. Ann Periodontol 1998; 3: 108-20.
17. Agerberth B, Gunne H, Odeberg J, Kogner P, Boman, HG, Gudmundsson GH. FALL-39, a putative human peptide antibiotic, is cycteine-free and expressed in bone marrow and testis. Proc Nalt Acad Sci USA 1995; 92: 195-9.
18. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, et al. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 1985; 76: 1427-35.
19. Lehrer RI, Ganz T. Antimicrobial peptides in mammalian and insect host defense. Cur Opin Immunol 1999; 11: 23-7.
20. Selsted ME, Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol 2005; 6: 551-7.
21. Fellermann K, Wehkamp J, Herrlinger KR, Stange EF. Crohn's disease: A defensin deficiency syndrome? Eur J Gastroenterol Hepatol 2003; 15: 627-34.
22. Wehkamp J, Fellermann K, Stange EF. Human defensins in Crohn's disease. Chem Immunol Allergy 2005; 86: 42-54.
23. Fellermann K, Wehkamp J, Stange EF. Antimicrobial peptides in the skin. N Engl J Med 2003; 348: 361-3.
24. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T. Endogeneous antimicrobial peptides and skin infections in atopic dermatitis. New Engl J Med 2002; 347: 1151-60.
25. Putsep K, Carlsson G, Boman HG, Andersson M. Dieficiency of antibacterial peptides in patients with morbus Kostmann: An observation study. Lancet 2002; 360: 1144-9.
26. Bowden GH. Microbiology of root surface caries in humans. J Dent Res 1990; 69(5): 1205-10.
27. Brook I. Microbiology and management of endodontic infections in children. J Clin Pediatr Dent 2003; 28(1): 13-7.
28. Kleinberg I. A mixed-bacteria ecological approach to understanding the role of the oral bacteria in dental caries causation: An alternative to Streptococcus mutans and the specific-plaque hypothesis. Crit Rev Oral Biol Med 2002; 13(2):108-25.
29. Kuramitsu HK. Virulence factors of mutans streptococci: Role of molecular genetics. Crit Rev Oral Biol Med 1993; 4: 159-76.
30. Takahashi I, Okahashi N, Matsushita K, Tokuda M, Kanamoto T, Munekata E, et al. Immunogenecity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen. J Immunol 1991; 146: 332-6.
31. Yamashita Y, Bowen WH, Burne RA, Kuramitsu. HK. Role of Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model. Infect Immun 1993; 61: 3811-7.
32. Hanada N, Kuramitsu HK. Isolation and characterization of the Streptococcus mutans gtfD gene, coding for primer-dependent soluble glucan synthesis, Infect Immun 1989; 57(7): 2079-85.
33. Nanbu A, Hayakawa M, Takada K, Shinozaki N, Abiko Y, Fukushima. K. Production, characterization, and application of monoclonal antibodies which distinguish four glucosyltransferases from Streptacoccus sobrinus. FEMS Immunol Med Microbiol 2000; 27: 9-15.
34. Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999; 4: 1-6.
35. Lindhe J, Liljenberg B, Listgarten M. Some microbiological and histopathological features of periodontal disease in man. J Periodontol 1980; 51: 264-9.
36. Moter A, Hoenig C, Choi BK, Riep B, Gobel UB. Molecular epidemiology of oral trepondines associated with periodontal disease. J Clin Microbiol 1998; 36: 1399-403.
37. Zambon JJ. Periodontal diseases: Microbial factors. Ann Periodontol 1996; 1: 879-925.
38. Curtis MA, Kuramitsu. HK, Lantz M, Macrina FL, Nakayama K, Potempa J, et al. Molecular genetics and nomenclature of proteases of Porphyromonas gingivalis. J Periodontal Res 1999; 34(8): 464-72.
39. Potempa J, Pavloff N, Travis J. Porphyromonas gingivalis: A proteinase/gene accounting adult. Trends Microbiol 1995; 3: 430-3.
40. Grenier D, Roy S, Chandad F, Plamondon P, Yoshioka M, Nakayama K, et al. Effect of inactivation of the Arg- and/or Lysgingipain gene on selected virulence and physiological properties of Porphyromonas gingivalis. Infect Immun 2003; 71(8): 4742-8.
41. Shi Y, Ratnayake DB, Okamoto K, Abe N, Yamamoto K, Nakayama K. Genetic analyses of proteolysis, hemoglobin-binding, and hemagglutination of Porphyromonas gingivalis: Construction of mutants with a combination of rgpA, rgpB, kgp and hagA. J Biol Chem 1999; 274: 17955-60.
42. Yoneda M, Hirofuji T, Anan H, Matsumoto A, Hamachi T, Nakayama K, et al. Mixed infection of Porphyromonas gingivalis and Bacteroides forsythus in a murine abscess model: Involvement of gingipains in a synergistic effect. J Periodontal Res 2001; 36(4): 237-43.
43. Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors of Porphyromonasi gingivalis. Periodontol 2000 1999; 20: 168-238.
44. Wang PL, Ohura K. Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. Crit Rev Oral Biol Med 2002; 13: 132-42.
45. Henderson B, Wilson M, Sharp L, Ward JM. Actinobacillus actinomycetemcomitans. J Med Microbiol 2002; 51: 1013-20.
46. Mandell RL, Socransky SS. A selective medium for Actinobacillus actinomycetemcomitans and the incidence of the organism in juvenile periodontitis. J Periodontol 1981; 52: 593-8.
47. Mayer DH, Fives-Taylor PM. The role of Actinobacillus actinomycetemcomitans in the pathogenesis of periodontal disease. Trends Microbiol 1997; 5: 224-8.
48. Slots J. Selective medium for isolation of Actinobacillus actinomy-cetemcomitans. J Clin Microbiol 1982; 15: 606-9.
49. Zambon JJ, Umemoto T, De Nardin E, Nakazawa F, Christersson LA, Genco RJ. Actinobacillus actinomycetemcomitans in the pathogenesis of human periodontal disease. Adv Dent Res 1988; 2: 269-74.
50. Asakawa R, Komatsuzawa H, Kawai T, Yamada S, Goncalves RB, Izumi S, et al. Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans. Mol Microbiol 2003; 50: 1125-39.
51. Kiley P, Holt SC. Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect Immun 1980; 30: 862-73.
52. Lally ET, Kieba IR, Demuth DR, Rosenbloom J, Golub EE, Taichman NS, et al.; Identification and expression of the Actinobacillus actinomycetemcomitans leukotoxin gene. Biochem Biophys Res Commun 1989; 159: 256-62.
53. Robertson PM, Lantz M, Marucha PT, Komman KS, Trummel CL, Holt SC. Collagenolytic activity associated with Bacteroides spp. and Actinobacillus actinomycetemcomitans. J Periodontal Res 1982; 17: 275-83.
54. Sugai M, Kawamoto T, Peres SY, Ueno Y, Komatsuzawa H, Fiujiwara T. et al., The cell cycle-specific growth-inhibitory factor produced by Actinobacillus actinomycetemcomitans is a cytolethal distending toxin. Infect Immun 1998; 66: 5008-19.
55. Riviere GR, Smith KS, Carranza JN, Tzagaroulaki E, Kay SL, Dock M. Subgingival distribution of Treponema denticola Treponema socranskii, and pathogen-related oral spirochetes: Prevalence and relationship to periodontal status of samples sites. J Periodontol 1995; 66: 829-37.
56. Slots J, Bragd L, Wilkstrom M, Dahlen G. The occurence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, and Bacteroides intermedius in destructive periodontal disease in adults. J Clin Periodontol 1986; 13: 570-7.
57. Nguyen TX, Cole AM; Lehrer RI. Evolution of primate. thetadefensins: A serpentine path to a sweet tooth. Peptides 2003; 24: 1647-54.
58. Cole AM, Hong T, Boo LM, Nguyen T, Zhao C, Bristol G, et al. Retrocyclin: A primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA 2002; 99: 1813-8.
59. Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: More than just microbicidal. Trends Immunol 2002; 23: 291-6
60. Cunliffe RN. alpha-defensins in the gastrointestinal tract. Mol Immunol 2003; 40:463-7.
61. Ganz T. Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes. Infect Immun 1987; 55: 568-71.
62. Jones DE, Bevins CL. Defensm-6 mRNA m human paneth cells: Implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett 1993; 315: 187-92.
63. Raj PA, Dentino AR. Current status of defensins and their role in innate and adaptive immunity. FEMS Microbiol Lett 2002; 206: 9-18.
64. Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol 1986; 60: 1068-74.
65. Huang HJ, Ross CR, Blecha F. Chemoattractant properties of PR-39, a neutrophil antibacterial peptide. J Leukoc Biol 1997; 61: 624-9.
66. Territo MC, Ganz T, Selstéd ME, Lehrer RI. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84: 2017-20.
67. Verbanac D, Zanetti M, Romeo D. Chemotactic and protease-inhibiting activities of antibiotic peptide precursors. FEBS Lett 1993;371:255-8.
68. Yang D, Chen Q, Chertov O, Oppenheim JJ. Human-neutrophil defensins selectively chemoattract native T and immature dendritic cells. J Leuk Biol 2000; 68: 9-14.
69. Abiko Y, Nishimura M, Kaku T. Defensins in saliva and the salivary glands. Med Electron Microsc 2003; 36: 247-52.
70. Dale BA, Krisanaprakomkit S, Defensin antimicrobial peptides in the oral cavity. J Oral Pathol Med 2001; 30: 321-7.
71. Dale BA, Kimball JR, Krisanaprakomkit S, Roberts F, Robinovitch M, ONeal R, et al., Localized antimicrobial peptide expression in human gingiva. J Periodontal Res 2001; 36: 285-94.
72. Devine DA. Antimicrobial peptides in, defence of the oral and respiratory tracts. Mol Immunol 2003; 40: 431-43.
73. McKay MS, Olson E, Hesla MA, Panyutich A, Ganz T., Perkins A, et al. Immunomagnetic recovery of human neutrophil defensins from the human gingival crevice. Oral Microbiol Immunol 1999; 14:190-3.
74. Dale BA, Tao R, Kimball JR, Jurevic RJ. Oral antimicrobial peptides and biological control of caries. BMC Oral Health 2006; 6: S13.
75. Tao R, Jurevic RJ, Coulton KK, Tsutsui MT, Roberts MC, Kimball JR, et al. Salivary antimicrobial peptide expression and dental caries experience in children. Antimicrob Agents Chemother 2005; 49: 3883-8
76. Bals R. Epithelial antimicrobial peptides in host defense against infection. Respir Res 2000; 1: 141-50.
77. Dunsche A, Acil Y, Dommisch Hea. The novel human beta-defensin-3 is widely expressed in oral tissues. Eur J Oral Sci 2002; 109: 121-4.
78. Garcia JR, Krause A, Schulz S, Rodriguez-Jimenez FJ, Kluver E, Adermann K, et al. Human beta-defensin 4: A novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 2001; 15: 1819-21.
79. Harder J, Bartels J, Christophers E, Schroder J-M. A peptide antibiotic from human skin. Nature 1997; 387: 861.
80. Harder J, Bartels J, Christopher E, Schroder J-M. Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 2001; 276: 5707-13.
81. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, et al. Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun 1999; 67: 2740-5.
82. Schroder J-M, Harder J. Human beta-defensin-2. Int J Biochem Cell Biol 1999; 31: 645-51.
83. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray Jr PB, Ganz T. Human β-defensin-1: An antimicrobial peptide of urogenital tissues. J Clin Invest 1998; 101: 1633-42.
84. Dinulos JGH, Mentele L, Fredericks LP, Dale BA, Darmstadt GL. Keratinocytes expression of human β-defensin 2 following bacterial infection: Role in cutaneous host defense. Clin Diag Lab Immunol 2003; 10: 161-6.
85. Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, et al. Human β-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 2002; 118: 275-81.
86. Midorikawa K, Ouhara K, Komatsuzawa H, Kawai T, Yamada S, Fujiwara T, et al. Staphylococcus aureus susceptibility to innate antimicrobial peptides, β-defensins and CAP 18, expressed by human keratinocytes. Infect Immun 2003; 71: 3730-9.
87. Sorensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T. Differential regulation of β-defensin expression in human skin by microbial stimuli. J Immunol 2005; 174: 4870-9.
88. Diamond G, Kaiser V, Rhodes J, Russell JP, Bevins CL. Transcriptional regulation of β-defensin gene expression in tracheal epithelial cells. Infect Immun 2000; 68: 113-9.
89. Liu L, Wang L, Jia HP, Zhao C, Heng HHQ, Schutte BC, et al. Structure and mapping of the human β-defensin HBD-2 gene and its expression at sites of inflammation. Gene 1998; 222: 237-44.
90. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway B-AD, et al. Production of β-defensins by human airway epithelia. Proc Natl Acad Sci USA 1998; 95: 14961-6.
91. Takahashi A, Wada A, Ogushi K, Maeda K, Kawahara T, Mawatari K, et al. Production of beta-defensin-2 by human colonic epithelial cells induced by Salmonella enteriddis flagella filament structural protein. FEBS Lett 2001; 508: 484-8.
92. Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, et al. The structure of human β-defensin-2 shows evidence of higher order oligomerization. J Biol Chem 2000; 275: 32911-8.
93. Hoover DM, Chertov O, Lubkowski J. The structure of human β-defensin-1. J Biol Chem 2001; 276: 39021-6.
94. Schibli DJ, Hunter HN, Aseyev V, Starner TD, Wiencek JM, McCray J, P. B., et al. The solution structure of the human β-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus. J Biol Chem 2002; 277: 8279-89.
95. Scott MG, Vreugdenhil ACE, Buurman WA, Hancock REW, Gold MR. Cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein. J Immunol 2000; 164: 549-53.
96. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002; 415: 389-95.
97. Harder J, Meyer-Hoffert U, Wehkamp K, Schwichtenberg L, Schroder J-M. Differential gene induction of human β-defensins (hBD- 1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J Invest Dermatol 2004; 123: 522-9.
98. Frye M, Bargon J, Gropp R. Expression of human beta-detensin-1 promotes differentiation of keratinocytes. J Mol Med 2001; 79: 275-82.
99. Niyonsaba F, Someya A, Hirata M, Ogawa H, Nagaoka I. Evaluation of the effects of peptide antibiotics human-β-defensin-1/2 and LL37 on histamine release and prostaglandin D2 production from mast cells. Eur J Immunol 2001; 31: 1066-75.
100. Yang D, Chertov O. Bykovskaia SN, Chen Q. Buffo MJ, Shogan J. et al. β-defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525-8.
101. Hosokawa I, Hosokawa Y, Komatsuzawa H, Goncalves RB, Karimbux N, Napimoga MH, et al. Innate immune Optide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue. Clin Exp Immunol 2006; 146(2): 218-25.
102. Krisanaprakornkit S, Weinberg A, Perezz CN, Dale BA. Expression of the peptide antibiotic human β-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun. 1998; 66: 4222-8
103. Becker MN, Diamond G, Verghese MW, Randell SH. CD14-dependent lipopolysaccharide-induced-β-defensin-2 expression in human tracheobronchial epithelium. J. Biol Chem 2000; 275: 29731-6.
104. Krisanaprakornkit S, Kimball JR, Weinberg A, Darveau RP, Bain-bridge AW, Dale BA. Inducible expression of human β-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: Multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect Immun.2000; 68: 2907-15.
105. Krisanaprakornkit S, Kimball JR, Dale BA. Regulation of human β-defensin-2 in gingival epithelial cells: The involvement of mitogen-activated protein kinase pathways, but not the NF-κB transcription factor family. J Inummol 2002; 168: 316-24.
106. Ouhara K, Komatsuzawa H, Shiba H, Uchida Y, Kawai T. Sayama K, et al. Actinobacillus actinomycetemcomitans outer membrane protein 100 triggers innate immunity and production of B-defensin and the 18-kilodalton cationic antimicrobial protein through the fibronectin-integrin pathway in human gingival epithelial cells. Infect Immun 2006; 74: 5211-20.
107. Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 1995; 63: 1291-7.
108. Zaiou M, Gallo RL. Cathelicidins, essential gene-encoded mammalian antibiotics. J Mol Med 2002; 80: 549-61.
109. Ramanathan B, Davis EG, Ross CR, Blecha F. Cathelicidins: Microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect 2002; 4: 361-72.
110. Bals R, Weiner DJ, Moscioni AD, Meegalla RL, Wilson JM. Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun 1999; 67: 6084-9.
111. Frohm M, Agerberth B, Ahangari G, Stahle-Backdahl M, Liden S, Wigzell H, et al. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocyle during-inflammatory disorders. J Biol Chem 1997; 272: 15258-63.
112. Malm J, Sorensen O. Persson T, Frohm-Nilsson M. Johansson B, Bjartell A, et al. The human cationic antimicrobial protein (hCAP-18) is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa. Infect Immun 2000; 68: 4297-302.
113. Murakami M, Ohtake T, Doraschner RA, Schittek B, Garbe C, Gallo RL. Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J. Invest Dermatol 2002; 119: 1090-5.
114. Nilsson MF, Sandstedt B, Sorensen O, Weber G, Borregaard N, Stahle-Backdahl M. The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6. Infect Immun 1999; 67: 1561-6.
115. Hirata M, Shimomura Y. Yoshida M, Morgan JG, Palings I, Wilson D, et al. Characterization of a rabbit cationic protein (CAP18) with lipopolysaccharide-inhibitory activiry. Infect Immun 1994; 62: 1421-6
116. Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, et al. Augumentation of the lipopolysaccharide-neutralizing activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by replacement with hydrophobic and cationic amino acid residues. Clin Diag Lab Immunol 2002; 9: 972-82.
117. Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, et al. Induction of keratinócyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL37. J Immunol 2005; 175(7): 4662-8.
118. Yang D, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J. LL37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 2000; 192: 1069-74.
119. Yang D, Chertov O, Oppenheim JJ. Participation of mammalian defensins and cathelicidins in antimicrobial immunity: Receptors and activities of human defensins and cathelicidin (LL-37). J Leuk Biol 2001; 69: 691-7.
120. Brogden KA. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 2005; 3(3): 238-50.
121. Sahl HG, Pag U, Bonness S, Wagner S, Antcheva. N, Tossi A. Mammalian defensins: Structures and mechanism of antibiotic activity. J Leuk Biol 2005; 77: 466-75.
122. Ouhara K, Komatsuzawa H, Yamada S, Shiba H, Fujiwara T, Ohara M, et al. Susceptibilities of periodontogenic and cariogenic bacteria to antibacterial peptides, beta-defensins and LL37, produced by human epithelial cells. J Antimicrob Chemother 2005; 55(6): 888-96.
123. Peschel A, Jack RW, Otto M, Collins LV, Staubitz P, Nicholson G, et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor mprF is based on modification of membrane lipids with L-lysine. J Exp Med 2001; 193: 1067-76.
124. Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI. Activities of LL37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 1998; 42: 2206-14.
125. Jia HP, Starner TD, Ackermann M, Kirby P, Tack BF, McCray PBJ. Abundant human beta-defensin-1 expression in milk and mammary gland epithelium. J Pediatr 2001; 138: 109-12.
126. O'Neil DA, Porter EM, Elewaut E, Anderson GM, Eckmann L, Ganz T, et al. Expression and regulation of the human ß-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol 1999; 163: 6718-24.
127. Goebel C, Mackay LG, Vickers ER, Mather LE. Detemination of defensin HNP-1, HNP-2, and HNP-3 in human saliva by using LC/MS. Peptides 2000; 21: 757-65.
128. Guthmiller JM, Vargas KG, Srikantha R, Schomberg LL, Weistroffer PL, McCray Jr. PB, et al. Susceptibilities of oral bacteria and yeast to mammalian cathelicidins. Antimicrob Agents Chemother 2001; 45: 3216-9.
129. Joly S, Maze C, McCray PBJ, Guthmiller JM. Human beta-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. J Clin Microbiol 2004; 42: 1024-9.
130. Maisetta G, Batoni G, Esin S, Raco G, Bottai D, Favilli F, et al. Susceptibility of Streptococcus mutans and Actinobacillus actinomycetemcomitans to bactericidal activity of human ß-defensin 3 in biological fluids. Antimicrob Agents Chemother 2005; 49: 1245-8.
131. Mineshiba F, Takashiba S, Mineshiba J, Matsuura K, Kokeguchi S, Murayama Y. Antibacterial activity of synthetic human ß-defensin-2 against periodontal bacteria. J Int Acad Periodontol 2003; 5: 35-40.
132. Nishimura E, Eto A, Kato M, Hashizume S, Imai S, Nisizawa T, et al. Oral streptococci exhibit diverse susceptibility to human beta-defensin-2: Antimicrobial effects of hBD-2 on oral streptococci. Curr Microbiol 2004; 48: 85-7.
133. Tanaka D, Miyasaki KT, Lehrer RI. Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL37: A cathelicidin found in human leukocytes and epithelium. Oral Microbiol Immunol 2003; 15: 226-31.
134. Brissette CA, Lukehart SA. Treponema denticola is resistant to human beta-defensins. Infect Immun 2002; 70: 3982-4.
135. Bader MW, Navarre WW, Shiau W, Nikaido H, Frye JG, McClelland M, et al. Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Mol Microbiol 2003; 50: 219-30
136. Bader MW, Sanowar S, Daley ME, Schneider AR, Cho U, Xu W, et al. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 2005; 122: 461-72.
137. Groisman EA, Mouslim C. Sensing by bacterial regulatory systems in host and non-host environments. Nat Rev Microbiol 2006; 4: 705-9.
138. Ernst RK, Yi EC, Guo L, Lim KB, Burns JL, Hackett M, et al. Specific lipopolysacchride found in cystic fibrosis airway Pseudomonas aeruginosa: Science 1999; 286: 1561-5.
139. Macfarlane ELA, Kwasnicka A, Hancock REW. Role of Pseudomonas aeruginosa PhoP-PhoQ in resistance to antimicrobial cationic peptides and aminoglycosides. Microbiology 2000; 146: 2543-54.
140. Banemann A, Deppisch H, Gross R. The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides. Infect Immun 1998; 66: 3607-12.
141. Rana FR, Macias EA, Sultany CM, Modzrakowski MC, Blazyk J. Interactions between magainin 2 and Salmonella typhimurium outer membranes: effect of lipopolysaccharide structure. J Biochem, 1991; 30: 5858-66.
142. Titarenko E, Lopez-Solanilla E, Garcia-Olmendo F, Rodriguez-Palenzuela P. Mutants of Ralstonia (Pseudomonas) solanacearum senseitive to antimicrobial peptides are altered in their lipopolysaccharide structure and are avirulent in tabacco. J Bacteriol 1997; 179: 6699-704.
143. Nishi H, Komatsuzawa H, Fujiwara T, McCallum N, Sugai M. Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus. Antimicrob Agents Chemother 2004; 48: 4800-7.
144. Peschel A, Otto M, Jack RW, Kaibacher H, Jung G, Gotz F. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 1999; 274: 8405-10.
145. Jin T, Bokarewa M, Foster T, Mitchell J, Higgins J, Tarkowski A. Staphylococcus aureus resists human defensins by production of Staphylokinase, a novel bacterial evasion mechanism. J Immunol 2004; 172: 1169-76.
146. Dalhammar G, Steiner H. Characterization of inhibitor A, a protease from Bacillus thuringiensis which degrades attacins and cecropins, two classes of antibacterial proteins in insects. Eur J Biochem 1984; 139: 247-52.
147. Devine DA, Marsh PD, Percival RS, Rangarajan M, Curtis MA. Modulation of antibacterial peptide activity by products of Porhyromonas gingivalis and Prevotella spp. Microbiology 1999; 145: 965-71.
148. Gunia T, Yi EC, Wang H, Hackett M, Miller SI. A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides. J Bacteriol 2000; 182: 4077-86.
149. Stumpe S, Schmid R, Stephens DL, Georgiou G, Bakker EP. Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing, cells of Escherichia coli. J Bacteriol 1998; 180: 4002-6.
150. Shafer WM, Qu X, Waring AJ, Lehrer RI. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc Natl Acad Sci USA 1998; 95: 1829-33.
151. Shelburne CE, Coulter WA, Olguin D, Lantz MS, Lopatin DE. Induction of ß-defensin resistance in the oral anaerobe Porphyromonas gingivalis. Antimicrob Agents Chemother 2005; 49: 183-7.
152. Cole AM, Waring AJ. The role of detensins in long biology and therapy. Am J Respir Med 2002; 1: 249-259.
153. Fu LM. The potential of human, neutrophil peptides in tuberculosis therapy. Int J Tuberc Lung Dis 2003; 7: 1027-32.
154. Klotman ME, Chang TL. Defensins in innate antiviral immunity. Nat Rev Immunol 2006; 6: 447-56.
155. Lupetti A, Danesi R, van't Wout JW, van Dissel JT, Senesi S, Nibbering PH. Antimicrobial peptides: Therapeutic potential for the treatment of Candida infections. Expert Opin Investig Drugs 2002; 11:309-18.
156. Bissell J, Joly S, Johnson GK, Organ CC, Dawson D, McCray Jr. PB, et al. Expression of ß-defensins in gingival health and in periodontal disease. J Oral Pathol Med 2004; 33: 278-85.
157. Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA. Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: High-throughout SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol 2003; 41: 90-6.
158. Brogden KA, Heidari M, Sacco RE, Palmquist D, Guthmiller JM, Johnson GK, et al. Defensin-induced adaptive immunity in mice and its potential in preventing periodontal disease. Oral Microbiol Immunol 2003; 18: 95-9.
159. Cirioni O, Giacometti A, Ghiselli R, Bergnach C, Orlando F, Silvestri C, et al. LL-37 protects rats against lethal sepsis caused by gram-negative bacteria. Antimicrob Agents Chemother 2006; 50: 1672-9
160. Huang GT, Zhang HB, Kim D, Liu L, Ganz T. A model for antimicrobial gene therapy: Demonstration of human-beta-defensin-2 antimicrobial activities in vivo. Hum Gene Ther 2002; 13: 2017-25.
161. Motzkus D, Schulz-Maronde S, Heitland A, Schulz A, Forssmann WG, Jubner M, et al. The novel beta-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo. FASEB J 2006; 20: 1701-2.
162. Yin C, Dang HN, Gazor F, Huang GT. Mouse salivary glands and human-beta-defensin-2 as a study model for antimicrobial gene therapy: technical considerations. Int J Antimicrob Agents 2006; 28: 352-60.
163. Zanetti M, Gennaro R, Skerlavaj B, Tomasinsig L, Circo R. Cathelicidin peptides as candidates for a novel class of antimicrobials. Curr Pharm Des 2002; 8: 779-93.
164. Cole AM, Lehrer RI. Minidefensins: Antimicrobial peptides with activity against HIV-1. Curr Pharm Des 2003; 9: 1463-73.
165. Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, et al. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 2002; 298: 995-1000.
166. DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell CM. Dental disease and risk of coronary heart disease and mortality. Br Med J 1993; 306: 688-91.
167. Grau AJ, Buggle F, Ziegler C, Schwarz W, Meuser J, Tasman AJ, et al. Association between acute cerebrovascular ischemia and chronic and recurrent infection. Stroke 1997; 28: 1724-9.
168. Herzberg MC, Meyer MW. Effects of oral flora on platelets: Possible consequences in cardiovascular disease. J Periodontol 1996; 67: 1138-42.
169. Joshipura KJ, Rimm EB, Douglass CW, Trichopoulos D, Ascherio A, Willett WC. Poor oral health and coronary heart disease. J Dent Res 1996; 75: 1631-6.
170. Kinane DF. Periodontal diseases' contributions to cardiovascular disease: An overview of potential mechanisms. Ann Periodontol 1998; 3: 142-50.
171. Lacassin F, Hoen B, Leport C, Selton-Suty C, Delahaye F, Goulet V, et al. Procedures associated with infective endocarditis in adults: A case control study. Eur Heart J 1995; 16: 1968-74.
172. Lorenz KA, Weiss PJ. Capnocytophagal pneumonia in a healthy man. West J Med 1994; 160: 79-80.
173. Morris JF, Sewell DL. Necrotizing pneumonia caused by mixed infection with Actinobacillus actinomycetemcomitans and Actinomyces israelii: Care report and review. Clin Infect Dis 1994; 18: 450-2
174. Scannapieco FA, Mylotte JM. Relationships between periodontal disease
175. Scannapieco FA, Papandonatos GD, Dunford RG. Associations between oral conditions and respiratory disease in a national sample survey population. Ann Periodontol 1998; 3: 251-6.
176. Shinzato T, Saito A. A mechanism of pathogenicity of "Streptococcus milleri group" in plumonary infection: Synergy with an anaerobe. J Med Microbiol 1994; 40: 118-23.
177. Yuan A, Luh KT, Yang PC. Actinobacillus actinomycetemcomitans pneumonia with possible septic embolization. Chest 1994; 105: 64.
178. Deshpande RG, Khan MB, Genco CA. Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis. Infect Immun 1998; 66: 5337-43.
179. Drangsholt MT. A new causal model of dental diseases associated with endocarditis. Ann Periodontol 1998; 3: 194-96.
180. Durack DT, Beeson PB, Petersdorf RG. Experimental bacterial endocarditis. 3. Production and progress of the disease in rabbits. Br J Exp Pathol 1973; 54: 142-51.
181. Overholser CD, Moreillon P, Glauser W. Experimental bacterial endocarditis after dental extractions in rats with periodontitis. J Infect Dis 1987; 155: 107-12.
182. Giles FJ, Miller CB, Hurd DD, Wingard JR, Fleming TR, Sonis ST, et al. A phase III, randomized, double-blind, placebo-controlled, multinational trial of iseganan for the prevention of oral mucositis in patients receiving stomatotoxic chemotherapy (PROMPT-CT trial). Leuk Lymphoma 2003; 44: 1165-72.
183. Tsai H, Bobek LA. Human salivary histatins: Promising anti-fungal therapeutic agents. Crit Rev Oral Biol Med 1998; 9: 480-97.
184. Nochi T, Kiyono H. Innate immunity in the mucosal immune system. Curr Pharm Des 2006; 12(32): 4203-13.
185. Salvi GE, Lang NP. The effects of non-steroidal anti-inflammatory drugs (selective and non-selective) on the treatment of periodontal diseases. Curr Pharm Des 2005; 11(14): 1757-69.
186. Wycoff KL. Secretory IgA antibodies from plants. Curr Pharm Des 2005; 11(19): 2429-37.