• Name: Devin Bolz, Ph.D.
  • Institution: Idaho Veterans Research and Education Foundation
  • Department: Research, Infectious Diseases
  • Phone: 208-422-1000 ext. 4143
  • Email: devin.bolz@va.gov

Summary: Research in my laboratory focuses on the study of bacterial pathogenesis, investigating the host response to infection and understanding the role of potent bacterial toxins in disease. I am currently involved in several exciting research projects in collaboration with the Infectious Disease Research group at the Boise VA Medical Center. One project, led by Dr. Dennis Stevens, is focused on defining molecular mechanisms of cardiac dysfunction associated with Streptococcal Toxic Shock Syndrome. This work consists of both in vitro studies, utilizing isolated cardiomyocytes, and in vivo animal studies to describe molecular responses of cardiac cells following interaction with Streptococcus pyogenes. My laboratory is also interested in improved treatments for infections caused by emerging multidrug-resistant bacterial pathogens, specificallyStaphylococcus aureus and Acinetobacter baumannii. Toward this goal, we have a project that investigates the impact of a novel oxazolidinone antibiotic on expression and production of S. aureus toxins. A second project focuses on the discovery of compounds which will inhibit essential virulence factors in Acinetobacter baumannii. Together, our laboratories’ analyses will be used to improve intervention strategies and reduce disease incidence of lethal and disabling infections. Minimum Classes: Basic cell biology, basic microbiology Projects: 1) Characterize matrix metalloproteinase (MMP) expression and activity in hearts of animals infected with Streptococcus pyogenes. The gram-positive human pathogenStreptococcus pyogenes (group A streptococcus; GAS) causes a variety of illnesses, ranging in severity from asymptomatic carriage to toxic shock syndrome. Notably, a subset of patients with Streptococcal Toxic Shock Syndrome develop a unique form of cardiomyopathy that leads to high rates of morbidity and mortality. Recent studies in our laboratory have shown that the GAS exotoxin, Streptolysin O, can cause profound myocardial dysfunction in isolated cardiomyocytes; however, mechanisms underlying the suppression of cardiac function in response to GAS remain largely unknown. Preliminary data from our lab supports that altered MMP expression could contribute to the development of cardiomyopathy. Thus, the goal of this summer project is to determine how matrix metalloproteinase expression/ activity in cardiac tissue is affected following exposure of animals to S. pyogenes and/or Streptolysin O.

  • Techniques that will be utilized include: bacterial culture and growth analysis, ribonucleic acid (RNA) isolation, quantitative real-time PCR, protein analysis (SDS-PAGE and Western blot analysis), zymography, immunohistochemistry, and confocal microscopy.

2) Analyze Staphylococcus aureus toxin expression following treatment with Tedizolid.Emerging antibiotic resistance poses a serious clinical challenge for the treatment of S. aureusinfections. In addition, several cell wall-active antibiotics have been shown to actually increase the expression of toxins which promote S. aureus pathogenesis. The goal of this summer project is to investigate S. aureus toxin expression following treatment with a novel oxazolidinone drug, Tedizolid, which recently received FDA approval for treatment of methicillin-resistant S. aureusskin infections. We are interested in defining the efficacy with which Tedizolid will attenuate S. aureus exotoxin production at subinhibitory doses and comparing the potency of this agent with other classes of antibiotics.

  • Techniques that will be utilized include: bacterial culture and growth analysis, ribonucleic acid (RNA) isolation, quantitative real-time PCR, protein analysis (SDS-PAGE and Western blot analysis), and enzyme-linked immunosorbent assay (ELISA).

3) Utilize antisense strategies to reduce the expression of essential genes in Acinetobacter baumannii. The goal of this summer project is to construct several recombinant plasmid vectors expressing antisense RNA in A. baumannii. Antisense technologies have become key tools for understanding how the expression of a specific gene contributes to a biological process. Specifically, the use of antisense technology in bacteria is remarkably powerful for identification of essential genes and for target-directed drug discovery. We are interested in developing inducible antisense RNA vectors that will target (i.e. reduce the expression of) a subset of essential genes in A. baumannii. Such constructs will allow us to control levels of protein expression for the selected targets and will be instrumental in assays seeking to identify inhibitors of target protein activity.

  • Techniques that will be utilized include: primer design, polymerase chain reaction (PCR), molecular cloning strategies, bacterial transformation, bacterial culture and growth analysis, inducible expression of antisense RNA, and quantitative real-time PCR.
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