Abstract

The pathogenic Neisseria are obligate human pathogens that rely on several antigenic variation systems to continually colonize and cause disease in the human population. This proposal will continue our studies into the molecular mechanisms used to promote pilin antigenic variation in Neisseria gonorrhoeae. High frequency changes in the pilin amino acid sequence are mediated by gene conversion reactions between one of 18 silent pilin copies and the single expressed pilin gene. In the next funding period we will continue to conduct our field-leading investigations into the molecular mechanisms require to effect high frequency gene conversion within the context of a bacterial chromosome. The results of these innovative studies will have great impact on the study of Neisserial pathogenesis, mechanisms of antigenic variation, DNA recombination and replication, and the role of alternative DNA structures on molecular processes in all cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI033493-28
Application #
10087840
Study Section
Special Emphasis Panel (NSS)
Program Officer
Vincent, Leah Rebecca
Project Start
1994-05-01
Project End
2023-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
28
Fiscal Year
2021
Total Cost
Indirect Cost

  Institution

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

  Publications

Obergfell, Kyle P; Schaub, Ryan E; Priniski, Lauren L et al. (2018) The low-molecular-mass, penicillin-binding proteins DacB and DacC combine to modify peptidoglycan cross-linking and allow stable Type IV pilus expression in Neisseria gonorrhoeae. Mol Microbiol :
Quillin, Sarah J; Hockenberry, Adam J; Jewett, Michael C et al. (2018) Neisseria gonorrhoeae Exposed to Sublethal Levels of Hydrogen Peroxide Mounts a Complex Transcriptional Response. mSystems 3:
Quillin, Sarah Jane; Seifert, H Steven (2018) Neisseria gonorrhoeae host adaptation and pathogenesis. Nat Rev Microbiol 16:226-240
Xu, Jing; Seifert, H Steven (2018) Analysis of Pilin Antigenic Variation in Neisseria meningitidis by Next-Generation Sequencing. J Bacteriol 200:
Seifert, H Steven (2017) Haemophilus spills its guts to make a biofilm. Proc Natl Acad Sci U S A 114:8444-8446
Palmer, Guy H; Bankhead, Troy; Seifert, H Steven (2016) Antigenic Variation in Bacterial Pathogens. Microbiol Spectr 4:
Château, Alice; Seifert, H Steven (2016) Neisseria gonorrhoeae survives within and modulates apoptosis and inflammatory cytokine production of human macrophages. Cell Microbiol 18:546-60
Obergfell, Kyle P; Seifert, H Steven (2016) The Pilin N-terminal Domain Maintains Neisseria gonorrhoeae Transformation Competence during Pilus Phase Variation. PLoS Genet 12:e1006069
Lenz, Jonathan D; Stohl, Elizabeth A; Robertson, Rosanna M et al. (2016) Amidase Activity of AmiC Controls Cell Separation and Stem Peptide Release and Is Enhanced by NlpD in Neisseria gonorrhoeae. J Biol Chem 291:10916-33
Rotman, Ella; Webber, David M; Seifert, H Steven (2016) Analyzing Neisseria gonorrhoeae Pilin Antigenic Variation Using 454 Sequencing Technology. J Bacteriol 198:2470-82

Showing the most recent 10 out of 67 publications