Greg Somerville, PhD

Greg Somerville, PhD
Associate Professor
155 Veterinary Biomedical Sciences
University of Nebraska-Lincoln
Lincoln, NE 68583-0903

Phone: (402) 472-6063
Email:
gsomerville3@unl.edu

 

Research Description

Environmental modulation of PIA synthesis. Staphylococcal medical device-associated infections usually involve a two-step process leading to the formation of a bacterial biofilm. The first step in biofilm formation involves attachment of the organism to an uncoated plastic surface, or a plastic surface coated with host proteins. The second step involves the accumulation of bacteria on top of the bacteria adhering to the plastic surface, a step requiring the production of polysaccharide intercellular adhesin (PIA). PIA synthesis is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same nutritional and stress conditions repress tricarboxylic acid (TCA) cycle activity; leading us to hypothesize that altering TCA cycle activity would affect PIA production. Confirmation of this hypothesis is based in part, on our observation that culturing S. epidermidis with a low concentration of a TCA cycle inhibitor (fluorocitric acid) dramatically increases PIA synthesis. Taken together, these data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, and/or the redox status of the bacteria. Currently, we are measuring the changes in intracellular metabolite pools that accompany the induction of PIA synthesis with the goal of identifying regulators capable of responding to these changes.

Posttranscriptional regulation of staphylococcal virulence. Staphylococcal aconitase is homologous (52% amino acid identity) to the bifunctional iron-responsive protein-1 (IRP-1). IRP-1 is a eukaryotic mRNA-binding protein that posttranscriptionally regulates the synthesis of iron-regulated proteins, and has aconitase enzymatic activity. Like IRP-1, aconitase from Bacillus subtilis and Escherichia coli can bind to and posttranscriptionally regulate mRNAs (Alen and Sonenshein 1999. Proc. Natl. Acad. Sci. 96:10412-10417; Tang and Guest 1999. Microbiology 145:3069-3079). These observations established bacterial aconitase, like IRP-1, as a bifunctional protein. In S. aureus, aconitase inactivation decreases production of virulence factors and enhances long-term survival relative to an isogenic strain. Some of the deleterious effects of aconitase inactivation are the result of the loss of enzymatic function (i.e., a metabolic block of the TCA cycle) and some are the result of the loss of regulatory function. We are conducting research to identify which effects of aconitase inactivation are the result of a metabolic defect and which are due to the loss of aconitase regulatory function.