Alkali generation, in the form of ammonia, is a major impediment to the initiation and progression of dental caries. There is also indirect evidence to support that ammonia production impacts calculus deposition by promoting mineral precipitation, and it may also exacerbate periodontal diseases by impairing the function of normal host immune and repair processes. There are two major sources of ammonia in the mouth: urea and arginine, which are hydrolyzed by ureases and the arginine deiminase system (ADS) of oral bacteria, respectively. During the previous funding periods, substantial insight was gained about the molecular architecture, genetic regulation, the role of ureases of oral bacteria in physiologic homeostasis and the importance of alkali generation in caries inhibition. This proposal builds on our previous studies with the ureases of oral bacteria, focusing on two fundamental areas directly related to the molecular biology, physiology and role in oral diseases of ammonia production. The first continues the studies we have developed during the previous funding periods on the molecular biology of urea catabolism by oral microorganisms and the second goal is to thoroughly characterize the arginine deiminase systems (ADS) of two oral streptococci. To accomplish our goals, we have organized the project under two specific aims:
Aim 1. Continued analysis of the genetics, physiology and role in oral ecology and disease of bacterial ureases focusing primarily i) on the pH- and carbohydrate-dependent expression of the urease of Streptococcus salivarius, but also ii) on the utility of recombinant, urease-producing bacteria in inhibition of dental caries and iii) on factors that may affect the ability of oral microorganisms to carry out ureolysis in the human oral cavity.
Aim 2. Molecular analysis of the arginine deiminase system of Streptococcus gordinii and Streptococcus rattus focusing i) on the cis- and trans-acting factors governing induction by arginine, and repression by glucose or oxygen, ii) analysis of the role of the ADS in inhibition of the initiation and progression of dental caries using of ADS-deficient mutants of S. gordonii and S. rattus, or recombinant, arginolytic S. mutans, and iii) physiological analysis of arginine transport and analysis of the effects of fluoride on alkali-generation via the ADS. This research will provide insights into new ways to control caries and other oral infectious diseases by manipulating the capacity or oral microorganisms to produce ammonia and to modulate the pH of oral biofilms.
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|Nascimento, M M; Liu, Y; Kalra, R et al. (2013) Oral arginine metabolism may decrease the risk for dental caries in children. J Dent Res 92:604-8|
|Burne, R A; Zeng, L; Ahn, S J et al. (2012) Progress dissecting the oral microbiome in caries and health. Adv Dent Res 24:77-80|
|Liu, Ya-Ling; Nascimento, Marcelle; Burne, Robert A (2012) Progress toward understanding the contribution of alkali generation in dental biofilms to inhibition of dental caries. Int J Oral Sci 4:135-40|
|Lemos, Jose A; Abranches, Jacqueline; Koo, Hyun et al. (2010) Protocols to study the physiology of oral biofilms. Methods Mol Biol 666:87-102|
|Toro, E; Nascimento, M M; Suarez-Perez, E et al. (2010) The effect of sucrose on plaque and saliva urease levels in vivo. Arch Oral Biol 55:249-54|
|Liu, Yaling; Burne, Robert A (2009) Multiple two-component systems modulate alkali generation in Streptococcus gordonii in response to environmental stresses. J Bacteriol 191:7353-62|
|Nascimento, M M; Gordan, V V; Garvan, C W et al. (2009) Correlations of oral bacterial arginine and urea catabolism with caries experience. Oral Microbiol Immunol 24:89-95|
|Griswold, A R; Nascimento, M M; Burne, R A (2009) Distribution, regulation and role of the agmatine deiminase system in mutans streptococci. Oral Microbiol Immunol 24:79-82|
|Liu, Yaling; Burne, Robert A (2009) Multiple two-component systems of Streptococcus mutans regulate agmatine deiminase gene expression and stress tolerance. J Bacteriol 191:7363-6|
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