Neisseria gonorrhoeae (Gc) is the sole cause of gonorrhea. One of the major virulence factors in Gc is the Type IV pilus. The pilus is directly involved in natural transformation, twitching motility, autoagglutination, and evasion of the host immune system. The pilus is a complex assembly of many different proteins and thought to be exported through the secretin PilQ, a dodecameric protein ring. PilQ is necessary for expression of the pilus, and thereforepilQ null mutants are defective for all pilus-dependent activities. Little work has been done to determine whether this secretin is directly involved in any of these pilin-dependent activities. The goal of this project is two-fold. First, using a previously developed error-prone PCR saturation mutagenesis method, determine which PilQ domains are required for multimerization, localization to the outer membrane, and pilus expression. Second, usingpilQ mutants derived from the first step, determine whether PilQ is directly involved in pilus-related pathogenic activities including autoagglutination, twitching motility, and natural transformation. If PilQ is shown to be directly involved in some or all of these, further analysis will be performed to determine which residues and/or domains are necessary for these interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI065091-03
Application #
7347531
Study Section
Special Emphasis Panel (ZRG1-F13 (20))
Program Officer
Hiltke, Thomas J
Project Start
2006-02-01
Project End
2009-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
3
Fiscal Year
2008
Total Cost
$53,992
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
Helm, R Allen; Seifert, H Steven (2010) Frequency and rate of pilin antigenic variation of Neisseria meningitidis. J Bacteriol 192:3822-3
Helm, R Allen; Seifert, H Steven (2009) Pilin antigenic variation occurs independently of the RecBCD pathway in Neisseria gonorrhoeae. J Bacteriol 191:5613-21
Helm, R Allen; Barnhart, Michelle M; Seifert, H Steven (2007) pilQ Missense mutations have diverse effects on PilQ multimer formation, piliation, and pilus function in Neisseria gonorrhoeae. J Bacteriol 189:3198-207