Adherence of Neisseria gonorrhoeae to host cells is a complex process which is initially mediated by Type IV pili. The pilus receptor on human cells has been identified as the complement regulatory protein, CD46. Four major isoforms of CD46 are produced on all human nucleated cells. The CD46 receptor interacts directly with gonococcal pili and appears to act as a signal transducer. Our preliminary results indicate that overall levels of CD46 on epithelial cells are inversely related to gonococcal adherence. This interesting observation has lead to several questions which will be investigated in this proposal. These questions include: do CD46 isoform levels correlate to gonococcal adherence, does the strength of calcium signaling via CD46 play a role in adherence, and how does pilin variation affect interaction with CD46 isoforms and signaling? This study will determine whether certain isoforms of CD46 are responsible for pilus-mediated adherence and whether differential signal transduction events via CD46 affect levels of adherence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI010568-03
Application #
6533983
Study Section
Special Emphasis Panel (ZRG1-BM-2 (02))
Program Officer
Quackenbush, Robert L
Project Start
2002-09-01
Project End
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$48,148
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Chen, Ching-ju; Tobiason, Deborah M; Thomas, Christopher E et al. (2004) A mutant form of the Neisseria gonorrhoeae pilus secretin protein PilQ allows increased entry of heme and antimicrobial compounds. J Bacteriol 186:730-9
Long, Cynthia D; Tobiason, Deborah M; Lazio, Matthew P et al. (2003) Low-level pilin expression allows for substantial DNA transformation competence in Neisseria gonorrhoeae. Infect Immun 71:6279-91
Tobiason, D M; Seifert, H S (2001) Inverse relationship between pilus-mediated gonococcal adherence and surface expression of the pilus receptor, CD46. Microbiology 147:2333-40