This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Streptococcus mutans is considered as the major etiological agent in dental caries. S. mutans is also an important agent of infective endocarditis. The organism colonizes the oral cavity by forming diverse, multispecies biofilms on the tooth surface, known as dental plaque. This pathogen has developed multiple mechanisms to adapt and to flourish in the hostile environment of the oral cavity. S. mutans has the ability to respond rapidly and efficiently to various environmental fluxes, including severe nutrient limitation, fluctuations in pH and temperature, and changes in oxidative and osmotic tensions. Exposure of bacteria to these adverse environments can induce a stress tolerance response through expression of a wide variety of genes that provides cross-protection against diverse environmental challenges. Stress tolerance genes are regulated by unique groups of transcriptional regulators, including alternate sigma factors. However, unlike other pathogens, S. mutans and other streptococci do not encode any alternate sigma factors. On the other hand, some genes that putatively function in stress responses in other bacteria are present in the S. mutans genome, but their role in stress and virulence has not been investigated in S. mutans in great detail. In this project, we plan to identify genes that are necessary for the organism to survive in the hostile environment of the oral cavity to cause tooth decay. Successful completion of our studies may lead to the development of novel therapeutic treatments for the prevention of tooth decay.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-8 (01))
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University of Kansas
Schools of Medicine
Kansas City
United States
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He, Chenchen; Duan, Shaofeng; Dong, Liang et al. (2017) Characterization of a novel p110?-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate 77:1187-1198
Li, Jiaqin; Wehmeyer, Graham; Lovell, Scott et al. (2016) 1.65?Å resolution structure of the AraC-family transcriptional activator ToxT from Vibrio cholerae. Acta Crystallogr F Struct Biol Commun 72:726-31
Ponnurangam, Sivapriya; Dandawate, Prasad R; Dhar, Animesh et al. (2016) Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells. Oncotarget 7:3217-32
Freitas, Natalia; Lukash, Tetyana; Dudek, Megan et al. (2015) Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks. Virus Res 205:12-21
Kumaraswamy, E; Wendt, K L; Augustine, L A et al. (2015) BRCA1 regulation of epidermal growth factor receptor (EGFR) expression in human breast cancer cells involves microRNA-146a and is critical for its tumor suppressor function. Oncogene 34:4333-46
Freitas, Natalia; Abe, Kenji; Cunha, Celso et al. (2014) Support of the infectivity of hepatitis delta virus particles by the envelope proteins of different genotypes of hepatitis B virus. J Virol 88:6255-67
Tang, Yuzhe; Chen, Ruibao; Huang, Yan et al. (2014) Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells. Mol Cancer Ther 13:1526-36
Freitas, Natalia; Cunha, Celso; Menne, Stephan et al. (2014) Envelope proteins derived from naturally integrated hepatitis B virus DNA support assembly and release of infectious hepatitis delta virus particles. J Virol 88:5742-54
Grogan, Patrick T; Sarkaria, Jann N; Timmermann, Barbara N et al. (2014) Oxidative cytotoxic agent withaferin A resensitizes temozolomide-resistant glioblastomas via MGMT depletion and induces apoptosis through Akt/mTOR pathway inhibitory modulation. Invest New Drugs 32:604-17
Alhakamy, Nabil A; Nigatu, Adane S; Berkland, Cory J et al. (2013) Noncovalently associated cell-penetrating peptides for gene delivery applications. Ther Deliv 4:741-57

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