David J. McGee

Dr. David J. McGee, Assistant Professor, received his Ph. D. in Microbiology and Immunology from Allegheny University of the Health Sciences (formerly Hahnemann University) in Philadelphia in 1997. At the University of Maryland he carried out postdoctoral training funded by the National Institutes of Health. He has served as an ad hoc reviewer on the Bacteriology and Mycology Study Section of NIH, and as an ad hoc reviewer of leading journals in microbiology. He joined the University of South Alabama College of Medicine faculty in 2001.

Helicobacter pylori pathogenesis, nitrogen metabolism, protein secretion and carcinogenesis

Helicobacter pylori is a fascinating helical-shaped, microaerophilic, motile, Gram-negative bacterium that spends most of its time in the harsh acidic environment of the stomach. A very successful and highly-adapted human 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 is the only bacterium that causes cancer and serves as a model for pathogen-induced carcinogenesis. The remarkable ability of this organism to cause these diverse disease manifestations over decades of infection is not well understood and our long-term goal is to cast light on this important public health problem. Our research may lead to novel insights into developing a desperately needed vaccine to prevent H. pylori infection and its sequelae.
We study several major virulence traits to better understand how these traits contribute to disease progression. One virulence trait is nitrogen metabolism. This bacterium spends a considerable amount of energy on synthesizing nitrogen metabolizing enzymes, including the very widely studied enzyme, urease, which functions to neutralize gastric acid. Other nitrogen metabolizing enzymes are not well studied. Our recent focus has been on arginase, a nitrogen-metabolizing enzyme that hydrolyzes arginine to urea and ornithine. We found that arginase is necessary for protection of H. pylori from acid and may contribute to the ability of H. pylori to colonize mice. We are now investigating the role of arginase in affecting host nitric oxide levels. Several current research projects we have include: i) purifying the arginase to study its biochemical features, including post-translational modifications of arginase, ii) study the arginase promoter regulation in an H. pylori background, iii) study the importance of other nitrogen metabolism enzymes in arginase activity, and iv) determine the importance of nitrogen metabolism enzymes, including arginase, in virulence. For virulence studies, we employ both tissue culture (gastric carcinoma cell lines) and animal models. Upon completion of these projects, we hope to have a better understanding of how arginase is regulated transcriptionally and post-translationally, and how arginase and other nitrogen metabolism proteins are involved in virulence.

A second virulence trait is the ability of H. pylori to secrete proteins. Protein secretion is a virulence trait common to many other bacterial pathogens, including E. coli, Yersinia, Salmonella, Campylobacter jejuni, and Shigella, but little is known about H. pylori secreted proteins. We have made an exciting breakthrough by growing this fastidious organism in chemically-defined medium lacking serum or proteins. Using this medium, we have observed about 30 secreted proteins and are identifying these proteins by amino acid sequence analysis. Several projects we have include: i) constructing mutants of H. pylori defective in secreted proteins, ii) purifying the secreted proteins and determining their amino acid sequence, and iii) determining the role these proteins play in virulence by determining colonization in animal models and by determining the effect of secreted proteins on host cell signal transduction pathways. Upon completion of these projects, we hope to have a better understanding of the identities and roles of H. pylori secreted proteins in virulence.
Our research program utilizes a multi-disciplinary approach to develop full insight into host-pathogen interactions and virulence mechanisms. We apply techniques from disciplines such as: in vivo experiments (gerbil and mouse models), proteomics, genomics, tissue culture, physiology and metabolism, immunology, genetics and molecular biology. Using only a few techniques may bias the results obtained and give an incomplete view of host-pathogen interactions.

Selected Recent Publications

Testerman T. L., D. J. McGee, and H. L. T. Mobley. 2001. Helicobacter pylori growth and urease detection in the chemically-defined medium Ham's F-12. J. Clin. Microbiol., 39:3842-3850.

Office Phone:	(251) 460-7134
Lab Phone:	(251) 460-7393
E-mail:	dmcgee@jaguar1.usouthal.edu

Robert N. Lausch

John E. Oakes