The overall objective of this proposal is to understand the genetic and environmental control of type I fimbriae expression. Type I fimbriae are a virulence factor associated with urinary tract infections in E. coli and are attractive to study because they are produced by the extremely well characterized strain, K-12. By studying K-12, we will utilize the extensive genetic tools available in this strain. Fimbrially-mediated attachment to host cells is considered an important step in infection. Fimbriae enable the bacteria to remain attached to the nutrient-rich host epithelium despite the constant flux of fluids. Nevertheless, fimbriae are also-excellent immunogens, and a significant metabolic drain on the bacterium. Therefore, the ability to control fimbrial expression appropriately is likely a virulence factor in itself. The proposed research will focus on the control of the DNA inversion (switch) associated with phase variation of type 1 fimbrial expression. Inversion of the fim switch requires fimB (ON-to-OFF or OFF-to-ON inversion) or fimE (ON-to-OFF inversion only), genes that likely encode the fim switch recombinases. Using molecular biological approaches, we intend to analyze the influence of genetic and environmental factors on fimB and fimE transcription and translation, and on the fim switch directly. The fim switch is also influenced by the global regulatory proteins H-NS and Lrp (Leucine-responsive regulatory protein), two proteins shown to influence the expression of other virulence determinants. The work suggested in this proposal is likely to provide a model with which to compare control of fim in clinical isolates. Moreover, this study should provide an insight into the genetic and environmental signals used to coordinately control virulence factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM050406-04
Application #
2519008
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1994-09-01
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106