The primary focus of this work involves elucidation of the pathogenic mechanisms associated with enteritis produced by Campylobacter jejuni. To date, very little is known concerning the virulence factors produced by this organism. Various pathogenic properties including, invasiveness and toxin production have been attributed to C. jejuni. However, the evidence for existence of such attributes is highly tentative. We have investigated both of these potential virulence factors using a variety of techniques. We believe we have established firmly, and for the first time, that C. jejuni is capable of entering and proliferating within cultured epithelia cells of intestinal origin. Further, C. jejuni can penetrate polarized epithelial cells in culture with kinetics that approach that of invasive strains of Salmonella and Yersinia. These studies suggest that adherence and internalization as observed in vitro are relevant pathogenic mechanisms associated with C. jejuni infection. We have characterized in detail the factors that influence these interactions and have further identified a fibronectin-binding protein on the surface of C. jejuni which may mediate attachment to intestinal epithelial cells. The amino-terminal amino acid sequence of this protein has been determined and has been used to generate oligonucleotide probes which are in turn being used to identify cloned gene sequences in a C. jejuni genomic library. We have also identified several new proteins that are synthesized by C. jejuni during intracellular residence. These appear to include members of the family of stress- response proteins. Other studies have failed to reveal any evidence for the production of enterotoxin-like molecules by C. jejuni as judged by a variety of immunologic, enzymatic, or biologic assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000553-03
Application #
3803242
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code