Lessons Learned from Clinical Studies: Roles of Mutans Streptococci in the Pathogenesis of Dental Caries

Current Oral Health Reports

Volumn 1, Issue 1, 2014, Pages 70-78

  Mattos Graner, Renata O ^a   Klein, Marlise I ^b   Smith, Daniel J ^c  

^a UNIVERSITY OF CAMPINAS   (Brazil)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^c FORSYTH INSTITUTE   (United States)

Author keywords

Cariogenic biofilm; Cariogenic organisms; Clinical studies; Dental caries; Mutans streptococci; Oral immune response; Streptococcus mutans

Indexed keywords

EID: 85007571212     PISSN: None     EISSN: 21963002     Source Type: Journal    
DOI: 10.1007/s40496-013-0008-1     Document Type: Review

References (102)

1. Tanzer JM. Dental caries is a transmissible infectious disease: the Keyes and Fitzgerald revolution. J Dent Res. 1995;74:1536–42. DOI: 10.1177/00220345950740090601
2. Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev. 1986;50:353–80.
3. Hamada S, Slade HD. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 1980;44:331–84.
4. Banas JA. Virulence properties of Streptococcus mutans. Front Biosci. 2004;9:1267–77. DOI: 10.2741/1305
5. Bowen WH, Koo H. Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res. 2011;45:69–86. Comprehensive review about the extracellular matrix of cariogenic biofilms. DOI: 10.1159/000324598
6. Lemos JA, Burne RA. A model of efficiency: stress tolerance by Streptococcus mutans. Microbiology. 2008;154:3247–55. DOI: 10.1099/mic.0.2008/023770-0
7. Tanzer JM, Livingston J, Thompson AM. The microbiology of primary dental caries in humans. J Dent Educ. 2001;65:1028–37.
8. Whiley RA, Beighton D. Current classification of the oral streptococci. Oral Microbiol Immunol. 1998;13:195–216. DOI: 10.1111/j.1399-302X.1998.tb00698.x
9. Nakano K, Nomura R, Nakagawa I, Hamada S, Ooshima T. Demonstration of Streptococcus mutans with a cell wall polysaccharide specific to a new serotype, k, in the human oral cavity. J Clin Microbiol. 2004;42:198–202. DOI: 10.1128/JCM.42.1.198-202.2004
10. van Houte J. Microbiological predictors of caries risk. Adv Dent Res. 1993;7:87–96.
11. Mattos-Graner RO, Correa MS, Latorre MR, Peres RC, Mayer MP. Mutans streptococci oral colonization in 12-30-month-old Brazilian children over a one-year follow-up period. J Public Health Dent. 2001;61:161–7. DOI: 10.1111/j.1752-7325.2001.tb03384.x
12. Alves AC, Nogueira RD, Stipp RN, Pampolini F, Moraes AB, Goncalves RB, et al. Prospective study of potential sources of Streptococcus mutans transmission in nursery school children. J Med Microbiol. 2009;58:476–81. DOI: 10.1099/jmm.0.005777-0
13. Mattos-Graner RO, Smith DJ, King WF, Mayer MP. Water-insoluble glucan synthesis by mutans streptococcal strains correlates with caries incidence in 12- to 30-month-old children. J Dent Res. 2000;79:1371–7. This study shows the influence of diversity in virulence-associated factors of S. mutans with disease activity in humans, further indicating that diversity in production of water-insoluble glucan influences S. mutans virulence. DOI: 10.1177/00220345000790060401
14. Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I, Dewhirst FE, et al. Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol. 2008;46:1407–17. DOI: 10.1128/JCM.01410-07
15. Gross EL, Beall CJ, Kutsch SR, Firestone ND, Leys EJ, Griffen AL. Beyond Streptococcus mutans: dental caries onset linked to multiple species by 16S rRNA community analysis. PLoS One. 2012;7:e47722. This paper includes longitudinal analysis of biofilm composition of young children to identify predictors of caries onset. Veillonella spp. was a predictor of caries lesions among initially healthy children. DOI: 10.1371/journal.pone.0047722
16. Tanner AC, Kent Jr RL, Holgerson PL, Hughes CV, Loo CY, Kanasi E, et al. Microbiota of severe early childhood caries before and after therapy. J Dent Res. 2011;90:1298–305. DOI: 10.1177/0022034511421201
17. de Carvalho FG, Silva DS, Hebling J, Spolidorio LC, Spolidorio DM. Presence of mutans streptococci and Candida spp. in dental plaque/dentine of carious teeth and early childhood caries. Arch Oral Biol. 2006;51:1024–8. DOI: 10.1016/j.archoralbio.2006.06.001
18. van Ruyven FO, Lingstrom P, van Houte J, Kent R. Relationship among mutans streptococci, “low-pH” bacteria, and lodophilic polysaccharide-producing bacteria in dental plaque and early enamel caries in humans. J Dent Res. 2000;79:778–84. DOI: 10.1177/00220345000790021201
19. Jenkinson HF, Lamont RJ. Oral microbial communities in sickness and in health. Trends Microbiol. 2005;13:589–95. DOI: 10.1016/j.tim.2005.09.006
20. Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res. 1994;8:263–71.
21. Smith DJ, Mattos-Graner RO. Secretory immunity following mutans streptococcal infection or immunization. Curr Top Microbiol Immunol. 2008;319:131–56.
22. Kristoffersson K, Grondahl HG, Bratthall D. The more Streptococcus mutans, the more caries on approximal surfaces. J Dent Res. 1985;64:58–61. DOI: 10.1177/00220345850640011101
23. Corby PM, Lyons-Weiler J, Bretz WA, Hart TC, Aas JA, Boumenna T, et al. Microbial risk indicators of early childhood caries. J Clin Microbiol. 2005;43:5753–9. DOI: 10.1128/JCM.43.11.5753-5759.2005
24. Torlakovic L, Klepac-Ceraj V, Ogaard B, Cotton SL, Paster BJ, Olsen I. Microbial community succession on developing lesions on human enamel. J Oral Microbiol. 2012;4. doi:10.3402/jom.v4i0.16125 DOI: 10.3402/jom.v4i0.16125
25. Becker MR, Paster BJ, Leys EJ, Moeschberger ML, Kenyon SG, Galvin JL, et al. Molecular analysis of bacterial species associated with childhood caries. J Clin Microbiol. 2002;40:1001–9. DOI: 10.1128/JCM.40.3.1001-1009.2002
26. Liu J, Wu C, Huang IH, Merritt J, Qi F. Differential response of Streptococcus mutans towards friend and foe in mixed-species cultures. Microbiology. 2011;157:2433–44. This paper proposes that Veillonella parvula strain enhances S. mutans ability to establish in biofilms. Transcriptomic analyses of S. mutans in co-cultures with V. parvula and its typical competitor species, S. gordonii indicate that V. parvula relieves S. mutans from the inhibitory functions of S. gordonii.
27. Kreth J, Zhang Y, Herzberg MC. Streptococcal antagonism in oral biofilms: Streptococcus sanguinis and Streptococcus gordonii interference with Streptococcus mutans. J Bacteriol. 2008;190:4632–40. DOI: 10.1128/JB.00276-08
28. Nyvad B, Kilian M. Comparison of the initial streptococcal microflora on dental enamel in caries-active and in caries-inactive individuals. Caries Res. 1990;24:267–72. DOI: 10.1159/000261281
29. Sansone C, van Houte J, Joshipura K, Kent R, Margolis HC. The association of mutans streptococci and non-mutans streptococci capable of acidogenesis at a low pH with dental caries on enamel and root surfaces. J Dent Res. 1993;72:508–16. DOI: 10.1177/00220345930720020701
30. Diaz PI, Chalmers NI, Rickard AH, Kong C, Milburn CL, Palmer Jr RJ, et al. Molecular characterization of subject-specific oral microflora during initial colonization of enamel. Appl Environ Microbiol. 2006;72:2837–48. DOI: 10.1128/AEM.72.4.2837-2848.2006
31. Svensater G, Borgstrom M, Bowden GH, Edwardsson S. The acid-tolerant microbiota associated with plaque from initial caries and healthy tooth surfaces. Caries Res. 2003;37:395–403. DOI: 10.1159/000073390
32. Willcox MD, Knox KW, Green RM, Drucker DB. An examination of strains of the bacterium Streptococcus vestibularis for relative cariogenicity in gnotobiotic rats and adhesion in vitro. Arch Oral Biol. 1991;36:327–33.
33. Willcox MD, Drucker DB, Green RM. In vivo dental plaque-forming ability and cariogenicity of the bacterium Streptococcus bovis in gnotobiotic rats. Arch Oral Biol. 1990;35:163–6.
34. Hamada S, Torii M, Kotani S, Tsuchitani Y. Adherence of Streptococcus sanguis clinical isolates to smooth surfaces and interactions of the isolates with Streptococcus mutans glucosyltransferase. Infect Immun. 1981;32:364–72.
35. Tamesada M, Kawabata S, Fujiwara T, Hamada S. Synergistic effects of streptococcal glucosyltransferases on adhesive biofilm formation. J Dent Res. 2004;83:874–9. DOI: 10.1177/154405910408301110
36. Vacca Smith AM, Scott-Anne KM, Whelehan MT, Berkowitz RJ, Feng C, Bowen WH. Salivary glucosyltransferase B as a possible marker for caries activity. Caries Res. 2007;41:445–50. DOI: 10.1159/000107930
37. Xu P, Alves JM, Kitten T, Brown A, Chen Z, Ozaki LS, et al. Genome of the opportunistic pathogen Streptococcus sanguinis. J Bacteriol. 2007;189:3166–75. DOI: 10.1128/JB.01808-06
38. Vacca-Smith AM, Bowen WH. Binding properties of streptococcal glucosyltransferases for hydroxyapatite, saliva-coated hydroxyapatite, and bacterial surfaces. Arch Oral Biol. 1998;43:103–10. DOI: 10.1016/S0003-9969(97)00111-8
39. Xiao J, Klein MI, Falsetta ML, Lu B, Delahunty CM, Yates 3rd JR, et al. The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm. PLoS Pathog. 2012;8:e1002623. This study demonstrates that a small population of S. mutans can modulate the development of a 3D matrix scaffold in mixed-species biofilms when sucrose is available. The presence of the matrix is essential for the creation of localized and highly acidic microenvironments throughout the biofilm 3D architecture. The acidic niches promote ecological shifts (favoring aciduric organisms such as S. mutans), while creating demineralizing sites at the tooth-enamel surface; these are critical for the onset of the dental caries disease. DOI: 10.1371/journal.ppat.1002623
40. Gregoire S, Xiao J, Silva BB, Gonzalez I, Agidi PS, Klein MI, et al. Role of glucosyltransferase B in interactions of Candida albicans with Streptococcus mutans and with an experimental pellicle on hydroxyapatite surfaces. Appl Environ Microbiol. 2011;77:6357–67. This paper proposes that S. mutans-derived Gtfs may mediate the association of C. albicans and cariogenic biofilm.
41. Alaluusua S, Renkonen OV. Streptococcus mutans establishment and dental caries experience in children from 2 to 4 years old. Scand J Dent Res. 1983;91:453–7.
42. Kohler B, Andreen I, Jonsson B, Hultqvist E. Effect of caries preventive measures on Streptococcus mutans and lactobacilli in selected mothers. Scand J Dent Res. 1982;90:102–8.
43. Kohler B, Andreen I. Influence of caries-preventive measures in mothers on cariogenic bacteria and caries experience in their children. Arch Oral Biol. 1994;39:907–11. DOI: 10.1016/0003-9969(94)90023-X
44. Kohler B, Andreen I. Mutans streptococci and caries prevalence in children after early maternal caries prevention: a follow-up at eleven and fifteen years of age. Caries Res. 2010;44:453–8. DOI: 10.1159/000320168
45. Kohler B, Andreen I. Mutans streptococci and caries prevalence in children after early maternal caries prevention: a follow-up at 19 years of age. Caries Res. 2012;46:474–80. This study describes the outcomes of the preventive program capable to interfere in MS transmission to children during the phase of increased risk of MS colonization that was described in reference 43. DOI: 10.1159/000339665
46. Caufield PW, Cutter GR, Dasanayake AP. Initial acquisition of mutans streptococci by infants: evidence for a discrete window of infectivity. J Dent Res. 1993;72:37–45. DOI: 10.1177/00220345930720010501
47. Fujiwara T, Sasada E, Mima N, Ooshima T. Caries prevalence and salivary mutans streptococci in 0-2-year-old children of Japan. Community Dent Oral Epidemiol. 1991;19:151–4. DOI: 10.1111/j.1600-0528.1991.tb00131.x
48. Cheon K, Moser SA, Wiener HW, Whiddon J, Momeni SS, Ruby JD, et al. Characteristics of Streptococcus mutans genotypes and dental caries in children. Eur J Oral Sci. 2013;121:148–55. DOI: 10.1111/eos.12044
49. Okada M, Taniguchi Y, Hayashi F, Doi T, Suzuki J, Sugai M, et al. Late established mutans streptococci in children over 3 years old. Int J Dent. 2010;2010:732468.
50. Nogueira RD, Alves AC, King WF, Goncalves RB, Hofling JF, Smith DJ, et al. Age-specific salivary immunoglobulin A response to Streptococcus mutans GbpB. Clin Vaccine Immunol. 2007;14:804–7.
51. Nogueira RD, Alves AC, Napimoga MH, Smith DJ, Mattos-Graner RO. Characterization of salivary immunoglobulin A responses in children heavily exposed to the oral bacterium Streptococcus mutans: influence of specific antigen recognition in infection. Infect Immun. 2005;73:5675–84. This study shows that intense and immunodominant responses to GbpB of S. mutans are highly prevalent among children who do not acquire S. mutans early in life in an SM-challenged population. DOI: 10.1128/IAI.73.9.5675-5684.2005
52. Caufield PW, Dasanayake AP, Li Y, Pan Y, Hsu J, Hardin JM. Natural history of Streptococcus sanguinis in the oral cavity of infants: evidence for a discrete window of infectivity. Infect Immun. 2000;68:4018–23. DOI: 10.1128/IAI.68.7.4018-4023.2000
53. Kohler B, Krasse B. Human strains of mutans streptococci show different cariogenic potential in the hamster model. Oral Microbiol Immunol. 1990;5:177–80. DOI: 10.1111/j.1399-302X.1990.tb00642.x
54. Gronroos L, Saarela M, Matto J, Tanner-Salo U, Vuorela A, Alaluusua S. Mutacin production by Streptococcus mutans may promote transmission of bacteria from mother to child. Infect Immun. 1998;66:2595–600. This study indicates the importance of bacteriocin production phenotypes in S. mutans competitiveness during oral colonization in humans.
55. Berkowitz RJ, Jordan HV, White G. The early establishment of Streptococcus mutans in the mouths of infants. Arch Oral Biol. 1975;20:171–4. DOI: 10.1016/0003-9969(75)90005-9
56. Berkowitz RJ. Mutans streptococci: acquisition and transmission. Pediatr Dent. 2006;28:106–9.
57. Saarela M, Alaluusua S, Takei T, Asikainen S. Genetic diversity within isolates of mutans streptococci recognized by an rRNA gene probe. J Clin Microbiol. 1993;31:584–7.
58. Kozai K, Nakayama R, Tedjosasongko U, Kuwahara S, Suzuki J, Okada M, et al. Intrafamilial distribution of mutans streptococci in Japanese families and possibility of father-to-child transmission. Microbiol Immunol. 1999;43:99–106. DOI: 10.1111/j.1348-0421.1999.tb02380.x
59. Li Y, Caufield PW. The fidelity of initial acquisition of mutans streptococci by infants from their mothers. J Dent Res. 1995;74:681–5. DOI: 10.1177/00220345950740020901
60. Mattos-Graner RO, Li Y, Caufield PW, Duncan M, Smith DJ. Genotypic diversity of mutans streptococci in Brazilian nursery children suggests horizontal transmission. J Clin Microbiol. 2001;39:2313–6. Provides evidence of horizontal transmission of MS. This paper shows that isolates from different children but with equal genotypic pattern show a nearly identical production of GtfB and GtfC in vitro. Thus, the genomic traits affecting virulence phenotypes are conserved after colonization of different hosts. DOI: 10.1128/JCM.39.6.2313-2316.2001
61. Emanuelsson IR, Li Y, Bratthall D. Genotyping shows different strains of mutans streptococci between father and child and within parental pairs in Swedish families. Oral Microbiol Immunol. 1998;13:271–7. DOI: 10.1111/j.1399-302X.1998.tb00707.x
62. Emanuelsson IR, Thornqvist E. Genotypes of mutans streptococci tend to persist in their host for several years. Caries Res. 2000;34:133–9. DOI: 10.1159/000016580
63. Klein MI, Florio FM, Pereira AC, Hofling JF, Goncalves RB. Longitudinal study of transmission, diversity, and stability of Streptococcus mutans and Streptococcus sobrinus genotypes in Brazilian nursery children. J Clin Microbiol. 2004;42:4620–6. DOI: 10.1128/JCM.42.10.4620-4626.2004
64. Ajdic D, McShan WM, McLaughlin RE, Savic G, Chang J, Carson MB, et al. Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc Natl Acad Sci U S A. 2002;99:14434–9. Landmark to study S. mutans biology. DOI: 10.1073/pnas.172501299
65. Zhang L, Foxman B, Drake DR, Srinivasan U, Henderson J, Olson B, et al. Comparative whole-genome analysis of Streptococcus mutans isolates within and among individuals of different caries status. Oral Microbiol Immunol. 2009;24:197–203. DOI: 10.1111/j.1399-302X.2008.00495.x
66. Waterhouse JC, Russell RR. Dispensable genes and foreign DNA in Streptococcus mutans. Microbiology. 2006;152:1777–88. DOI: 10.1099/mic.0.28647-0
67. Cornejo OE, Lefebure T, Bitar PD, Lang P, Richards VP, Eilertson K, et al. Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans. Mol Biol Evol. 2013;30:881–93. This study shows that the S. mutans genomes are dynamically altered but have a core genome not present in non-MS streptococci.
68. Argimon S, Caufield PW. Distribution of putative virulence genes in Streptococcus mutans strains does not correlate with caries experience. J Clin Microbiol. 2011;49:984–92. DOI: 10.1128/JCM.01993-10
69. Stipp RN, Goncalves RB, Hofling JF, Smith DJ, Mattos-Graner RO. Transcriptional analysis of gtfB, gtfC, and gbpB and their putative response regulators in several isolates of Streptococcus mutans. Oral Microbiol Immunol. 2008;23:466–73. DOI: 10.1111/j.1399-302X.2008.00451.x
70. Saxena D, Li Y, Caufield PW. Identification of unique bacterial gene segments from Streptococcus mutans with potential relevance to dental caries by subtraction DNA hybridization. J Clin Microbiol. 2005;43:3508–11. DOI: 10.1128/JCM.43.7.3508-3511.2005
71. Mattos-Graner RO, Jin S, King WF, Chen T, Smith DJ, Duncan MJ. Cloning of the Streptococcus mutans gene encoding glucan binding protein B and analysis of genetic diversity and protein production in clinical isolates. Infect Immun. 2001;69:6931–41. This study associates biofilm formation with amounts of GbpB produced in clinical strains.
72. Palmer SR, Miller JH, Abranches J, Zeng L, Lefebure T, Richards VP, et al. Phenotypic heterogeneity of genomically-diverse isolates of Streptococcus mutans. PLoS One. 2013;8:e61358. Analyses of 15 clinical S. mutans strains revealed that this species developed several strategies to thrive in the oral cavity that can influence dental caries pathogenesis. DOI: 10.1371/journal.pone.0061358
73. Mattos-Graner RO, Napimoga MH, Fukushima K, Duncan MJ, Smith DJ. Comparative analysis of Gtf isozyme production and diversity in isolates of Streptococcus mutans with different biofilm growth phenotypes. J Clin Microbiol. 2004;42:4586–92. DOI: 10.1128/JCM.42.10.4586-4592.2004
74. Duque C, Stipp RN, Wang B, Smith DJ, Hofling JF, Kuramitsu HK, et al. Downregulation of GbpB, a component of the VicRK regulon, affects biofilm formation and cell surface characteristics of Streptococcus mutans. Infect Immun. 2011;79:786–96. DOI: 10.1128/IAI.00725-10
75. Nakajo K, Takahashi N, Beighton D. Resistance to acidic environments of caries-associated bacteria: Bifidobacterium dentium and Bifidobacterium longum. Caries Res. 2010;44:431–7. DOI: 10.1159/000318582
76. Napimoga MH, Kamiya RU, Rosa RT, Rosa EA, Hofling JF, Mattos-Graner R, et al. Genotypic diversity and virulence traits of Streptococcus mutans in caries-free and caries-active individuals. J Med Microbiol. 2004;53:697–703. DOI: 10.1099/jmm.0.05512-0
77. Argimon S, Alekseyenko AV, DeSalle R, Caufield PW. Phylogenetic analysis of glucosyltransferases and implications for the coevolution of mutans streptococci with their mammalian hosts. PLoS One. 2013;8:e56305. DOI: 10.1371/journal.pone.0056305
78. Smith EG, Spatafora GA. Gene regulation in S. mutans: complex control in a complex environment. J Dent Res. 2012;91:133–41.
79. Stephenson K, Hoch JA. Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Pharmacol Ther. 2002;93:293–305. DOI: 10.1016/S0163-7258(02)00198-5
80. Biswas I, Drake L, Erkina D, Biswas S. Involvement of sensor kinases in the stress tolerance response of Streptococcus mutans. J Bacteriol. 2008;190:68–77. DOI: 10.1128/JB.00990-07
81. Song L, Sudhakar P, Wang W, Conrads G, Brock A, Sun J, et al. A genome-wide study of two-component signal transduction systems in eight newly sequenced mutans streptococci strains. BMC Genomics. 2012;13:128. DOI: 10.1186/1471-2164-13-128
82. Klein MI, Bang S, Florio FM, Hofling JF, Goncalves RB, Smith DJ, et al. Genetic diversity of competence gene loci in clinical genotypes of Streptococcus mutans. J Clin Microbiol. 2006;44:3015–20. DOI: 10.1128/JCM.02024-05
83. Stipp RN, Boisvert H, Smith DJ, Hofling JF, Duncan MJ, Mattos-Graner RO. CovR and VicRK regulate cell surface biogenesis genes required for biofilm formation in Streptococcus mutans. PLoS One. 2013;8:e58271. DOI: 10.1371/journal.pone.0058271
84. Rolla G, Iversen OJ, Bonesvoll P. Lipoteichoic acid - the key to the adhesiveness of sucrose grown Streptococcus mutans. Adv Exp Med Biol. 1978;107:607–17. DOI: 10.1007/978-1-4684-3369-2_69
85. Klein MI, Xiao J, Lu B, Delahunty CM, Yates III JR, Koo H. Streptococcus mutans protein synthesis during mixed-species biofilm development by high-throughput quantitative proteomics. PLoS One. 2012;7:e45795. The assembly of the exopolysaccharide-rich matrix and the concomitant development of acidic niches appear to modulate the regulation of stress survival pathways by S. mutans. GtfB, GtfC and glucan-binding proteins are all induced, leading to continuous biofilm accretion and development of a favorable milieu for the survival and growth of cariogenic organisms. DOI: 10.1371/journal.pone.0045795
86. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 6th ed. Saunders Elsevier; 2007.
87. Brandtzaeg P. Do salivary antibodies reliably reflect both mucosal and systemic immunity? AnnNY Acad Sci. 2007;1098:288–311. DOI: 10.1196/annals.1384.012
88. Robinette RA, Oli MW, McArthur WP, Brady LJ. Beneficial immunomodulation by Streptococcus mutans anti-P1 monoclonal antibodies is Fc independent and correlates with increased exposure of a relevant target epitope. J Immunol. 2009;183:4628–38. DOI: 10.4049/jimmunol.0803300
89. Nogueira RD, Sesso ML, Borges MC, Mattos-Graner RO, Smith DJ, Ferriani VP. Salivary IgA antibody responses to Streptococcus mitis and Streptococcus mutans in preterm and fullterm newborn children. Arch Oral Biol. 2012;57:647–53. DOI: 10.1016/j.archoralbio.2011.11.011
90. Ito T, Maeda T, Senpuku H. Roles of salivary components in Streptococcus mutans colonization in a new animal model using NOD/SCID.e2f1−/− mice. PLoS One. 2012;7:e32063. DOI: 10.1371/journal.pone.0032063
91. King WF, Chen T, Nogueira R, Mattos-Graner R, Smith DJ. Epitopes shared among pioneer oral flora and Streptococcus mutans GbpB. In: Sasano T, Suzuki O, editors. Interface oral health. Tokyo: Springer; 2009. p. 416–7.
92. Parisotto TM, King WF, Duque C, Mattos-Graner RO, Steiner-Oliveira C, Nobre-Dos-Santos M, et al. Immunological and microbiologic changes during caries development in young children. Caries Res. 2011;45:377–85. DOI: 10.1159/000330230
93. Bratthall D, Serinirach R, Hamberg K, Widerstrom L. Immunoglobulin A reaction to oral streptococci in saliva of subjects with different combinations of caries and levels of mutans streptococci. Oral Microbiol Immunol. 1997;12:212–8. DOI: 10.1111/j.1399-302X.1997.tb00381.x
94. ten Cate JM, Zaura E. The numerous microbial species in oral biofilms: how could antibacterial therapy be effective? Adv Dent Res. 2012;24:108–11. DOI: 10.1177/0022034512450028
95. Taubman MA, Nash DA. The scientific and public-health imperative for a vaccine against dental caries. Nat Rev Immunol. 2006;6:555–63. This paper states the case for the potential benefit of active immunization, especially in a public health context.
96. Liang S, Hosur KB, Nawar HF, Russell MW, Connell TD, Hajishengallis G. In vivo and in vitro adjuvant activities of the B subunit of Type IIb heat-labile enterotoxin (LT-IIb-B5) from Escherichia coli. Vaccine. 2009;27:4302–8.
97. Taubman MA, Smith DJ, Lees A. Preparation and immunogenicity of monoepitopic and polyepitopic tetanus toxoid-glucosyltransferase peptide conjugate vaccines. IADR 81st General Session, Goteborg, Sweden, J Dent Res. 2003, 82B, Abst. 227.
98. Jia R, Guo JH, Fan MW, Bian Z, Chen Z, Peng B, et al. Mucosal immunization against dental caries with plasmid DNA encoding pac gene of Streptococcus mutans in rats. Vaccine. 2004;22:2511–6. DOI: 10.1016/j.vaccine.2004.01.025
99. Liu F, Yang J, Zhang Y, Zhou D, Chen Y, Gai W, et al. Recombinant flagellins with partial deletions of the hypervariable domain lose antigenicity but not mucosal adjuvancy. Biochem Biophys Res Commun. 2010;392:582–7. DOI: 10.1016/j.bbrc.2010.01.077
100. Shi W, Li YH, Liu F, Yang JY, Zhou DH, Chen YQ, et al. Flagellin enhances saliva IgA response and protection of anti-caries DNA vaccine. J Dent Res. 2012;91:249–54. DOI: 10.1177/0022034511424283
101. Ma JK, Hikmat BY, Wycoff K, Vine ND, Chargelegue D, Yu L, et al. Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med. 1998;4:601–6. DOI: 10.1038/nm0598-601
102. Kruger C, Hultberg A, van Dollenweerd C, Marcotte H, Hammarstrom L. Passive immunization by lactobacilli expressing single-chain antibodies against Streptococcus mutans. Mol Biotechnol. 2005;31:221–31. This paper presents a novel method for passive immunization against S. mutans infection. DOI: 10.1385/MB:31:3:221