A selected group of oral bacteria commonly associated with dental health is capable of producing alkali via the arginine deiminase system (ADS), which has a profound impact on the pH of human oral biofilms. An increased risk for dental caries has been associated with reduced ADS activity of the bacteria in oral biofilms. Arginolytic bacterial strains from dental plaque samples of caries-free and caries-active adults were isolated and characterized to investigate the basis for differences in plaque ADS activity between individuals. Fifty-six ADS-positive bacterial strains were identified by 16S rRNA gene sequencing, and their ADS activity levels were compared under standard growth conditions. The spectrum of bacterial ADS activity ranged from 45.2 to 688.0 units (mg protein)-1. Although Streptococcus sanguinis was the most prevalent species, other Streptococcus sp. were also represented. Biochemical assays carried out using 27 ADS-positive strains under conditions known to induce or repress ADS gene expression showed substantial variation in arginolytic activity in response to pH, oxygen and the availability of carbohydrate or arginine. This study reveals that the basis for the wide spectrum of arginolytic expression observed among clinical strains is, at least in part, attributable to differences in the regulation of the ADS within and between species. The results provide insights into the microbiological basis for intersubject differences in ADS activity in oral biofilms and enhance our understanding of dental caries as an ecologically driven disease in which arginine metabolism moderates plaque pH and promotes dental health.

1.
Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I, Dewhirst FE, Leys EJ, Paster BJ: Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol 2008;46:1407-1417.
2.
Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE: Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 2005;43:5721-5732.
3.
Acevedo AM, Machado C, Rivera LE, Wolff M, Kleinberg I: The inhibitory effect of an arginine bicarbonate/calcium carbonate cavistat-containing dentifrice on the development of dental caries in Venezuelan school children. J Clin Dent 2005;16:63-70.
4.
Acevedo AM, Montero M, Rojas-Sanchez F, Machado C, Rivera LE, Wolff M, Kleinberg I: Clinical evaluation of the ability of cavistat in a mint confection to inhibit the development of dental caries in children. J Clin Dent 2008;19:1-8.
5.
Becker MR, Paster BJ, Leys EJ, Moeschberger ML, Kenyon SG, Galvin JL, Boches SK, Dewhirst FE, Griffen AL: Molecular analysis of bacterial species associated with childhood caries. J Clin Microbiol 2002;40:1001-1009.
6.
Burne R, Liu Y, Zeng L: Acid tolerance strategies of commensal and pathogenic oral streptococci. Soc Gen Microbiol Autumn 2010 Meet, Nottingham, 2010.
7.
Burne RA, Marquis RE: Alkali production by oral bacteria and protection against dental caries. FEMS Microbiol Lett 2000;193:1-6.
8.
Burne RA, Parsons DT, Marquis RE: Environmental variables affecting arginine deiminase expression in oral streptococci; in Dunny G, Cleary P, McKay L (eds): Genetics and Molecular Biology of Streptococci, Lactococci, and Enterococci. Washington, American Society for Microbiology, 1991.
9.
Burne RA, Wen ZT, Chen YY, Penders JE: Regulation of expression of the fructan hydrolase gene of Streptococcus mutans gs-5 by induction and carbon catabolite repression. J Bacteriol 1999;181:2863-2871.
10.
Casiano-Colon A, Marquis RE: Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance. Appl Environ Microbiol 1988;54:1318-1324.
11.
Clancy KA, Pearson S, Bowen WH, Burne RA: Characterization of recombinant, ureolytic Streptococcus mutans demonstrates an inverse relationship between dental plaque ureolytic capacity and cariogenicity. Infect Immun 2000;68:2621-2629.
12.
Corby PM, Lyons-Weiler J, Bretz WA, Hart TC, Aas JA, Boumenna T, Goss J, Corby AL, Junior HM, Weyant RJ, Paster BJ: Microbial risk indicators of early childhood caries. J Clin Microbiol 2005;43:5753-5759.
13.
Crielaard W, Zaura E, Schuller AA, Huse SM, Montijn RC, Keijser BJ: Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health. BMC Med Genomics 2011;4:22.
14.
Dawes C, Dibdin GH: Salivary concentrations of urea released from a chewing gum containing urea and how these affect the urea content of gel-stabilized plaques and their pH after exposure to sucrose. Caries Res 2001;35:344-353.
15.
Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG: The human oral microbiome. J Bacteriol 2010;192:5002-5017.
16.
Dong Y, Chen YY, Burne RA: Control of expression of the arginine deiminase operon of Streptococcus gordonii by CcpA and Flp. J Bacteriol 2004;186:2511-2514.
17.
Golub LM, Borden SM, Kleinberg I: Urea content of gingival crevicular fluid and its relation to periodontal diseases in humans. J Periodont Res 1971;6:243-251.
18.
Gross EL, Leys EJ, Gasparovich SR, Firestone ND, Schwartzbaum JA, Janies DA, Asnani K, Griffen AL: Bacterial 16S sequence analysis of severe caries in young permanent teeth. J Clin Microbiol 2010;48:4121-4128.
19.
Huang X, Exterkate RA, Ten Cate JM: Factors associated with alkali production from arginine in dental biofilms. J Dent Res 2012;91:1130-1134.
20.
Kleinberg I: Biochemistry of the dental plaque. Adv Oral Biol 1970;4:43-90.
21.
Kleinberg I, Jenkins GN: The pH of dental plaques in the different areas of the mouth before and after meals and their relationship to the pH and rate of flow of resting saliva. Arch Oral Biol 1964;72:493-516.
22.
Kopstein J, Wrong OM: The origin and fate of salivary urea and ammonia in man. Clin Sci Mol Med 1977;52:9-17.
23.
Kraivaphan P, Amornchat C, Triratana T, Mateo LR, Ellwood R, Cummins D, Devizio W, Zhang YP: Two-year caries clinical study of the efficacy of novel dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 p.p.m. fluoride. Caries Res 2013;47:582-590.
24.
Liu Y, Burne RA: Multiple two-component systems modulate alkali generation in Streptococcus gordonii in response to environmental stresses. J Bacteriol 2009;191:7353-7362.
25.
Liu Y, Dong Y, Chen YY, Burne RA: Environmental and growth phase regulation of the Streptococcus gordonii arginine deiminase genes. Appl Environ Microbiol 2008;74:5023-5030.
26.
Mager DL, Ximenez-Fyvie LA, Haffajee AD, Socransky SS: Distribution of selected bacterial species on intraoral surfaces. J Clin Periodontol 2003;30:644-654.
27.
Margolis HC, Duckworth JH, Moreno EC: Composition and buffer capacity of pooled starved plaque fluid from caries-free and caries-susceptible individuals. J Dent Res 1988;67:1476-1482.
28.
Marquis RE: Oxygen metabolism, oxidative stress and acid-base physiology of dental plaque biofilms. J Ind Microbiol 1995;15:198-207.
29.
Marquis RE, Bender GR, Murray DR, Wong A: Arginine deiminase system and bacterial adaptation to acid environments. Appl Environ Microbiol 1987;53:198-200.
30.
Nascimento MM, Gordan VV, Garvan CW, Browngardt CM, Burne RA: Correlations of oral bacterial arginine and urea catabolism with caries experience. Oral Microbiol Immunol 2009;24:89-95.
31.
Nascimento MM, Liu Y, Kalra R, Perry S, Adewumi A, Xu X, Primosch RE, Burne RA. Oral arginine metabolism may decrease the risk for dental caries in children. J Dent Res 2013; 92:604-608.
32.
Paster BJ, Boches SK, Galvin JL, Ericson RE, Lau CN, Levanos VA, Sahasrabudhe A, Dewhirst FE: Bacterial diversity in human subgingival plaque. J Bacteriol 2001;183:3770-3783.
33.
Peterson S, Woodhead J, Crall J: Caries resistance in children with chronic renal failure: plaque pH, salivary pH, and salivary composition. Pediatr Res 1985;19:796-799.
34.
Rogers AH: Utilization of nitrogenous compounds by oral bacteria. Aust Dent J 1990;35:468-471.
35.
Russell RR: How has genomics altered our view of caries microbiology? Caries Res 2008;42:319-327.
36.
Schulte R, Burne RA, Gordan VV, Nascimento MM: Alkali generation capacity of oral bacteria (abstract 113). IADR/AADR/CADR 87th General Session, Miami, 2009.
37.
Shu M, Morou-Bermudez E, Suarez-Perez E, Rivera-Miranda C, Browngardt CM, Chen YY, Magnusson I, Burne RA: The relationship between dental caries status and dental plaque urease activity. Oral Microbiol Immunol 2007;22:61-66.
38.
Sissons CH, Hancock EM, Cutress TW: The source of variation in ureolysis in artificial plaques cultured from human salivary bacteria. Arch Oral Biol 1988a;33:721-726.
39.
Sissons CH, Hancock EM, Perinpanayagam HE, Cutress TW: The bacteria responsible for ureolysis in artificial dental plaque. Arch Oral Biol 1988b;33:727-733.
40.
Sissons CH, Wong L, Hancock EM, Cutress TW: The pH response to urea and the effect of liquid flow in ‘artificial mouth' microcosm plaques. Arch Oral Biol 1994;39:497-505.
41.
Srisilapanan P, Korwanich N, Yin W, Chuensuwonkul C, Mateo LR, Zhang YP, Cummins D, Ellwood RP: Comparison of the efficacy of a dentifrice containing 1.5% arginine and 1,450 p.p.m. fluoride to a dentifrice containing 1,450 p.p.m. fluoride alone in the management of early coronal caries as assessed using quantitative light-induced fluorescence. J Dent 2013;41:29-34.
42.
Stephan RM: Changes in hydrogen-ion concentration on tooth surfaces and in carious lesions. J Am Dent Assoc 1940;27:718-723.
43.
Van Wuyckhuyse BC, Perinpanayagam HE, Bevacqua D, Raubertas RF, Billings RJ, Bowen WH, Tabak LA: Association of free arginine and lysine concentrations in human parotid saliva with caries experience. J Dent Res 1995;74:686-690.
44.
Vander Wauven C, Pierard A, Kley-Raymann M, Haas D: Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway. J Bacteriol 1984;160:928-934.
45.
Wijeyeweera RL, Kleinberg I: Arginolytic and ureolytic activities of pure cultures of human oral bacteria and their effects on the pH response of salivary sediment and dental plaque in vitro. Arch Oral Biol 1989;34:43-53.
46.
Yin W, Hu DY, Fan X, Feng Y, Zhang YP, Cummins D, Mateo LR, Pretty IA, Ellwood RP: A clinical investigation using quantitative light-induced fluorescence (QLF) of the anticaries efficacy of a dentifrice containing 1.5% arginine and 1,450 p.p.m. fluoride as sodium monofluorophosphate. J Clin Dent 2013a;24(A):15-22.
47.
Yin W, Hu DY, Li X, Fan X, Zhang YP, Pretty IA, Mateo LR, Cummins D, Ellwood RP: The anti-caries efficacy of a dentifrice containing 1.5% arginine and 1,450 p.p.m. fluoride as sodium monofluorophosphate assessed using quantitative light-induced fluorescence (QLF). J Dent 2013b;41:22-28.
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