Gulig, Paul A: Professor
My research interests are on the molecular pathogenesis of bacterial-host interactions – both beneficial and in disease. I am interested in how the bacterium Oxalobacter formigenes prevents kidney stones by stimulating the intestinal epithelium to transport oxalate, the component of most kidney stones, from the blood into the intestinal lumen. In terms of disease, I have studied Vibrio vulnificus, which rapidly kills people after they eat raw oysters or get contaminated wounds, but that project in now purely collaborative with colleagues in other departments and institutions.
For over 30 years, my career has been studying molecular pathogenesis, the use of genetic manipulation of microorganisms to understand the way that they cause disease. My newest project involves molecular genetic analysis of a beneficial bacterium with goal of improving human health.
I am interested in determining how Oxalobacter formigenes, a member of the normal flora of the human intestines, stimulates the gut epithelium to transport oxalate from the blood into the intestinal lumen, where the bacteria use it as their sole energy source. In doing this, the urinary levels of oxalate and thereby the likelihood of kidney stones are reduced. I am using molecular genetic manipulation of the bacterial genome and animal models to determine the molecular mechanism by which O. formigenes stimulates oxalate transport. We are using transposon mutagenesis, genomic sequencing, and allelic exchange mutagenesis to identity bacterial mutants that are defective at reducing urinary oxalate when they colonize mice that are fed an oxalate-supplemented diet. Once the genes encoding oxalate transport stimulation and their products are identified, we hope to develop improved O. formigenes strains to serve as improved probiotics and/or to develop drugs that stimulate oxalate transport to prevent kidney stones.
V. vulnificus infection is noted for the extensive tissue damage that occurs after ingestion of vibrios in raw oysters or contamination of wounds, high mortality (50%), and rapid progression (death within days). V. vulnificus avoids phagocytosis, replicates extensively in the interstitial fluid, and then causes damage, most likely by the secretion of a plethora of extracellular factors. We are focusing our studies on how the vibrios replicate so rapidly, how they avoid the host defenses, and how they cause damage in such a short period of time, 24 hours after infection. We developed a mouse model which reproduces the important characteristics of human disease, including predisposing conditions and tissue damage. We have used this model to perform comparative analysis of numerous V. vulnificus strains of both clinical and environmental origin. We are using molecular genetic tools, including signature-tagged mutagenesis and alkaline phosphatase fusion/insertion mutagenesis, to identify virulence genes using this animal model. Additionally, we have developed a marker plasmid tool to enable the differentiation of growth versus death of different vibrio strains or mutants in the animal host. We have performed genomic DNA sequencing to identify genes that are shared or unique to highly virulent and attenuated strains, and we are using allelic exchange mutagenesis to delete candidate virulence genes and examine their effects on virulence. This project is on hold while we focus our research efforts on the Oxalobacter project.
Post Doctoral Fellow, Washington University
Ph.D., University of Texas Southwestern Medical Center
B.S., Texas A&M University
Awards, Professional Service:
Editorial Board – Infection and Immunity
BMS 6300 Fundamentals of Microbiology and Immunology
BMS 6020 Clinical Neuroscience
BMS 6131 Hematology
BMS 6634 Gastroenterology and Hepatology
BMS 6635 Dermatology and the Musculoskeletal System
BMS 6642 Respiratory Systems
GMS 6038 Bacterial Genetics and Physiology
GMS 6108 Bacterial Physiology, Antibiotics, and Genetics
GMS 6121 Infectious Diseases
GMS 7192 Journal Colloquy
Chair, UF Institutional Biosafety Committee
Member, UF Graduate Curriculum Committee
Member, State Course Numbering System Committee