Staphylococcus aureus has historically been a leading cause of nosocomial infections in humans worldwide. In the past several decades the emergence of methicillin-resistant S. aureus (MRSA) harboring multiple antibiotic resistance determinants has left relatively few therapeutic options available. Today, these strains have made their way into the community and now pose a very serious public health threat, causing more deaths per year than HIV-AIDS. The University of Nebraska Medical Center has committed to advancing research into the staphylococci with the hiring of several new researchers, and the concerted collaboration with regional investigators, who are all focused on this important pathogen. These researchers have expertise in varied aspects of the staphylococci including: biofilm development, gene regulation, physiology, and the immunology of staphylococcal infections. The hypothesis to be tested by this team in this application is that S. aureus biofilm formation involves complex developmental processes that affect the host immune response. The application includes four projects centered around staphylococcal biofilm and disease including: regulated cell death during biofilm development (Project 1, K. Bayles);effect of arginine metabolism on biofilm formation in the staphylococci (Project 2, P. Fey);the role of nuclease in biofilm development and disease (Project 3, A. Horswill);and innate immunity to S. aureus biofilm (Project 4, T. Kielian). The cores include: Biofilm Growth and Analysis Core (Core A, J. Bose);Bioimaging Core (Core B, T. Fritz);and Administrative Core (Core C, K. Bayles). Each project involves highly collaborative and synergistic research endeavors and relies heavily on the cores. These efforts will have a dramatic impact on our understanding of biofilm formation in the staphylococci and the effect it has on the host response. Ultimately, these studies will pave the way for novel therapeutic approaches for the treatment of staphylococcal infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-TS-M (M1))
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Huntley, Clayton C
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University of Nebraska Medical Center
Schools of Medicine
United States
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Yamada, Kelsey J; Kielian, Tammy (2018) Biofilm-Leukocyte Cross-Talk: Impact on Immune Polarization and Immunometabolism. J Innate Immun :1-9
Bhinderwala, Fatema; Lonergan, Samantha; Woods, Jade et al. (2018) Expanding the Coverage of the Metabolome with Nitrogen-Based NMR. Anal Chem 90:4521-4528
Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica et al. (2018) Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence. J Orthop Res 36:1605-1613
Svechkarev, Denis; Sadykov, Marat R; Bayles, Kenneth W et al. (2018) Ratiometric Fluorescent Sensor Array as a Versatile Tool for Bacterial Pathogen Identification and Analysis. ACS Sens 3:700-708
Yamada, Kelsey J; Heim, Cortney E; Aldrich, Amy L et al. (2018) Arginase-1 Expression in Myeloid Cells Regulates Staphylococcus aureus Planktonic but Not Biofilm Infection. Infect Immun 86:
King, Alyssa N; Borkar, Samiksha; Samuels, David J et al. (2018) Guanine limitation results in CodY-dependent and -independent alteration of Staphylococcus aureus physiology and gene expression. J Bacteriol :
Mlynek, Kevin D; Sause, William E; Moormeier, Derek E et al. (2018) Nutritional Regulation of the Sae Two-Component System by CodY in Staphylococcus aureus. J Bacteriol 200:
Gries, Casey M; Kielian, Tammy (2017) Staphylococcal Biofilms and Immune Polarization During Prosthetic Joint Infection. J Am Acad Orthop Surg 25 Suppl 1:S20-S24
Krute, Christina N; Rice, Kelly C; Bose, Jeffrey L (2017) VfrB Is a Key Activator of the Staphylococcus aureus SaeRS Two-Component System. J Bacteriol 199:
Moormeier, Derek E; Bayles, Kenneth W (2017) Staphylococcus aureus biofilm: a complex developmental organism. Mol Microbiol 104:365-376

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