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, includig 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.
As a leading cause of indwelling medical device-related infections, the study of Staphylococcus aureus biofilm formation and its impact on its host is critical to reducing the burden of this pervasive pathogen to our healthcare system. The collaborative efforts of our studies seek to identify the mechanisms responsible for the alteration of the host immune response to favor an anti-inflammatory environment that is more permissive for bacterial persistence. Overall, the results of these studies hold promise for the development of improved strategies to treat S. aureus biofilm-related infections.
|Ibberson, Carolyn B; Parlet, Corey P; Kwiecinski, Jakub et al. (2016) Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection. Infect Immun 84:1917-29|
|Marshall, Darrell D; Sadykov, Marat R; Thomas, Vinai C et al. (2016) Redox Imbalance Underlies the Fitness Defect Associated with Inactivation of the Pta-AckA Pathway in Staphylococcus aureus. J Proteome Res 15:1205-12|
|Kavanaugh, Jeffrey S; Horswill, Alexander R (2016) Impact of Environmental Cues on Staphylococcal Quorum Sensing and Biofilm Development. J Biol Chem 291:12556-64|
|Gries, Casey M; Sadykov, Marat R; Bulock, Logan L et al. (2016) Potassium Uptake Modulates Staphylococcus aureus Metabolism. mSphere 1:|
|Windham, Ian H; Chaudhari, Sujata S; Bose, Jeffrey L et al. (2016) SrrAB Modulates Staphylococcus aureus Cell Death through Regulation of cidABC Transcription. J Bacteriol 198:1114-22|
|Chaudhari, Sujata S; Thomas, Vinai C; Sadykov, Marat R et al. (2016) The LysR-type transcriptional regulator, CidR, regulates stationary phase cell death in Staphylococcus aureus. Mol Microbiol 101:942-53|
|Vidlak, Debbie; Kielian, Tammy (2016) Infectious Dose Dictates the Host Response during Staphylococcus aureus Orthopedic-Implant Biofilm Infection. Infect Immun 84:1957-65|
|Paharik, Alexandra E; Horswill, Alexander R (2016) The Staphylococcal Biofilm: Adhesins, Regulation, and Host Response. Microbiol Spectr 4:|
|Schaeffer, Carolyn R; Hoang, Tra-My N; Sudbeck, Craig M et al. (2016) Versatility of Biofilm Matrix Molecules in Staphylococcus epidermidis Clinical Isolates and Importance of Polysaccharide Intercellular Adhesin Expression during High Shear Stress. mSphere 1:|
|Lewis, April M; Rice, Kelly C (2016) Quantitative Real-Time PCR (qPCR) Workflow for Analyzing Staphylococcus aureus Gene Expression. Methods Mol Biol 1373:143-54|
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