Streptococcus mutans is the primary etiological agent of dental caries, a costly and ubiquitous health problem worldwide. The ability of this organism to cause disease depends on its abilities to adhere to the tooth surface, form tenacious biofilms and tolerate acid and other detrimental conditions in the oral cavity. We previously showed that the biofilm regulatory protein A (BrpA) plays a major role in regulation of acid- and oxidative-stress tolerance and biofilm formation in S. mutans. Deficiency of BrpA dramatically increased the susceptibility of the deficient mutants to acid-killing and hydrogen peroxide challenge. The BrpA-deficient mutant was able to bind to and form microcolonies on a surface, but failed to accumulate and develop mature biofilms. Predicted as a surface-associated protein, BrpA is a glycoprotein and possesses compositional and structural features that appear to be unique to S. mutans in the oral flora. Therefore, BrpA has great potential as a candidate for drug and vaccine production that may eliminate S. mutans from the plaque without disrupting other beneficial microorganisms in the flora. This study is designed to further investigate BrpA in regards to the (i) cellular location and structure-function relationships, (ii) regulation of expression in response to environmental stimuli, and (iii) role in the adherence, persistence and competitiveness of S. mutans when grown in mixed-species biofilms. The information derived from this study will contribute to a better understanding of the role and the underlying mechanism of BrpA in regulation of S. mutans pathogenicity and will enrich our knowledge on the ecology of the oral flora. More importantly, the data derived from this study could facilitate the design of therapeutic and preventive strategies to combat dental caries and possibly infective endocarditis.

Public Health Relevance

The ability of Streptococcus mutans to cause dental caries depends on its ability to adhere to and form tenacious biofilms on the tooth surface and to tolerate detrimental conditions in the oral cavity. Glycoprotein BrpA in S. mutans plays major roles in environmental stress tolerance and formation of biofilms. This study will further investigate the role and the underlying mechanisms of BrpA in regulation of S. mutans pathogenicity and the potential for targeting BrpA in anti-caries strategy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE019452-04
Application #
8282949
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$347,936
Indirect Cost
$102,911
Name
Louisiana State Univ Hsc New Orleans
Department
Dentistry
Type
Schools of Dentistry
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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Wen, Zezhang T; Bitoun, Jacob P; Liao, Sumei (2015) PBP1a-deficiency causes major defects in cell division, growth and biofilm formation by Streptococcus mutans. PLoS One 10:e0124319
Baker, J L; Derr, A M; Karuppaiah, K et al. (2014) Streptococcus mutans NADH oxidase lies at the intersection of overlapping regulons controlled by oxygen and NAD+ levels. J Bacteriol 196:2166-77
Liao, Sumei; Klein, Marlise I; Heim, Kyle P et al. (2014) Streptococcus mutans extracellular DNA is upregulated during growth in biofilms, actively released via membrane vesicles, and influenced by components of the protein secretion machinery. J Bacteriol 196:2355-66
Zhang, J F; Wu, R; Fan, Y et al. (2014) Antibacterial dental composites with chlorhexidine and mesoporous silica. J Dent Res 93:1283-9
Bitoun, Jacob P; Liao, Sumei; Xie, Gary G et al. (2014) Deficiency of BrpB causes major defects in cell division, stress responses and biofilm formation by Streptococcus mutans. Microbiology 160:67-78
Bitoun, Jacob P; Liao, Sumei; McKey, Briggs A et al. (2013) Psr is involved in regulation of glucan production, and double deficiency of BrpA and Psr is lethal in Streptococcus mutans. Microbiology 159:493-506
Bitoun, J P; Liao, S; Yao, X et al. (2012) BrpA is involved in regulation of cell envelope stress responses in Streptococcus mutans. Appl Environ Microbiol 78:2914-22
Bitoun, Jacob P; Liao, Sumei; Yao, Xin et al. (2012) The redox-sensing regulator Rex modulates central carbon metabolism, stress tolerance response and biofilm formation by Streptococcus mutans. PLoS One 7:e44766

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