The primary objectives of this project are to provide greater insight into the control of eDNA generation (through autolysis) and processing (via staphylococcal nuclease) within a biofilm. These studies will focus on the varied micro-niches that exist within a staphylococcal biofilm, and define the metabolic and stoichiometric factors that influence the expression of genes involved in these processes during biofilm development. The proposed studies will extend our preliminary results testing the hypothesis that S. aureus biofilm produces distinct functional subpopulations in response to environmental and stochastic effects on gene expression. In testing this hypothesis we will establish and elucidate the functional roles of different functional subpopulations within a mature biofilm. To achieve these goals, we will perform three specific aims.
The first aim will utilize a variety of transcriptional and metabolic probes, in combination with BioFlux microfluidics technology, to investigate the metabolic heterogeneity that arises during biofilm development and its impact on death and lysis.
The second aim will study the regulation of nuclease expression during biofilm development, focusing heavily on the role of the Sae regulatory system, and the novel hypothesis that SaeP is a sensor of eDNA.
The third aim will establish a division of labor within a biofilm and define the functional roles of the different subpopulations within a biofilm, including dispersal, mutagenesis, and antibiotic tolerance. Overall, the experiments described in these specific aims will rely on a highly collaborative effort to yield greater insight into the environmental and stochastic regulatory mechanisms that dictate the metabolism of different biofilm niches. In addition to providing a more complete understanding of the metabolic processes inherent to staphylococcal biofilm, this project will foster a burgeoning perspective of bacterial biofilm as a highly complex population of differentiated cells, akin to multicellular organisms.
|Moormeier, Derek E; Bayles, Kenneth W (2017) Staphylococcus aureus biofilm: a complex developmental organism. Mol Microbiol 104:365-376|
|Nicholson, Tracy L; Brockmeier, Susan L; Sukumar, Neelima et al. (2017) The Bordetella Bps Polysaccharide Is Required for Biofilm Formation and Enhances Survival in the Lower Respiratory Tract of Swine. Infect Immun 85:|
|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|
|Markley, John L; Brüschweiler, Rafael; Edison, Arthur S et al. (2017) The future of NMR-based metabolomics. Curr Opin Biotechnol 43:34-40|
|Mashruwala, Ameya A; Gries, Casey M; Scherr, Tyler D et al. (2017) SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative Biofilm Formation in Staphylococcus aureus. Infect Immun 85:|
|Paharik, Alexandra E; Kotasinska, Marta; Both, Anna et al. (2017) The metalloprotease SepA governs processing of accumulation-associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis. Mol Microbiol 103:860-874|
|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:|
|Zhang, Xinyan; Bayles, Kenneth W; Luca, Sorin (2017) Staphylococcus aureus CidC Is a Pyruvate:Menaquinone Oxidoreductase. Biochemistry 56:4819-4829|
|Halsey, Cortney R; Lei, Shulei; Wax, Jacqueline K et al. (2017) Amino Acid Catabolism in Staphylococcus aureus and the Function of Carbon Catabolite Repression. MBio 8:|
|Mishra, Surabhi; Horswill, Alexander R (2017) Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting Staphylococcus aureus Biofilm Formation. mSphere 2:|
Showing the most recent 10 out of 98 publications