Office Phone: 318-675-8138
Laboratory Phone: 318-675-8139
Office Fax: 318-675-5764
Postdoctoral Study, University of Maryland-Baltimore
Ph.D., Microbiology and Immunology, 1997, Allegheny University of the Health Sciences (now Drexel University)
B.S., Microbiology, 1992, Philadelphia College of Pharmacy and Science (now University of the Sciences in Philadelphia)
Helicobacter pylori and Arcanobacterium haemolyticum Host-Pathogen Interactions
Helicobacter pylori is a fascinating bacterium that thrives in the stressful acidic environment of the human stomach. A very successful and highly-adapted pathogen, H. pylori infects about 50% of the world's population, causing an extraordinary range of disease severity-- from gastritis and peptic ulcers to gastric cancer and MALT lymphoma. H. pylori thus serves as a model for pathogen-induced carcinogenesis. Disease severity is dependent on genes produced by the bacterium, genetic polymorphisms of the host, and environmental influences (eg., diet), making this organism an exciting challenge to unravel these various contributors to disease processes. Our long-term goal is to unravel the mechanisms by which H. pylori causes these diverse disease manifestations.
Our recent interest has centered on understanding the contributions of host cholesterol to H. pylori response to stress and the role of cholesterol in H. pylori pathogenesis. H. pylori steals host cholesterol, modifies it and the organism decorates its surface with these modified cholesterol derivatives, rendering the organism resistant to antimicrobial agents, bile salts, acid and oxidative stress. The organism changes its LPS profiles in response to cholesterol. Our research may lead to novel insights into host-pathogen interactions and aid in development of a desperately needed vaccine or anti-Helicobacter therapy to prevent H. pylori infection and its sequelae.
Arcanobacterium haemolyticum is a Gram positive rod that is an emerging pathogen. It causes pharyngitis in adolescents and wound infections. Our understanding of this organism’s physiology, metabolism and virulence are almost completely unknown. Several recently initiated projects include random sequence analysis of the genome, proteomics of organisms grown under different conditions, establishment of a tissue culture model, and characterization of the hemolysin, arcanolysin (ALN). We aim to understand the mechanisms by which this poorly studied organism causes disease.
Trainor, E. A., K. E. Horton, T. L. Testerman, P. B. Savage, and D. J. McGee. 2011. Helicobacter pylori displays cholesterol-dependent resistance to ceragenins and bile salts: Role of the HefC efflux pump. Infect. Immun., 79: 88-97. PMID: 20974830.
McGee, D. J., A. E. George, E. A. Trainor, K. E. Horton, E. Hildebrandt and T. L. Testerman. 2011. Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37. Antimicrobial Agents Chemo., 55:2897-2904. PMID: 21464244. *Article featured as Journal Highlights in ASM’s publication Microbe.
Jost, B. H., E. A. Lucas, S. J. Billington, A. J. Ratner*, D. J. McGee*. 2011. Arcanolysin is a cholesterol- dependent cytolysin of the human pathogen Arcanobacterium haemolyticum. BMC Microbiology, 11: 239. *Co-corresponding authors. PMID: 22029628.
Kim, S. H., R. A. Sierra, D. J. McGee*, and J. Zabaleta*. 2012. Transcriptional profiling and cytokine/chemokine analysis of gastric epithelial cells infected with wild type or arginase (rocF)-deficient Helicobacter pylori. BMC Microbiology 12: 175 (9 pages) 10.1186/1471-2180-12-175. * Co-corresponding authors. PMID: 22889111.
Shimomura, H., K. Hosoda, D. J. McGee, S. Hayashi, K. Yokota, and Y. Hirai. 2013. A novel role of cholesterol glucosylation: detoxification of 7-dehydrocholesterol fatal to Helicobacter pylori. J. Bacteriology, 195: 359-367. PMID: 23144252.
Ruther, H. S., K. Phillips, D. Ross, A. Crawford, M. P. Weidner, O. Sammra, C. Lammler, and D. J. McGee. 2015. Smooth and rough biotypes of Arcanobacterium haemolyticum can be genetically distinguished at the arcanolysin locus. PLOS One 10(9):e0137346. PMCID: 26382754.