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.

Public Health Relevance

  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 #
4R37AI033493-25
Application #
9319938
Study Section
Special Emphasis Panel (NSS)
Program Officer
Vincent, Leah Rebecca
Project Start
1994-05-01
Project End
2023-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
25
Fiscal Year
2018
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
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
Peak, Ian R; Chen, Adrienne; Jen, Freda E-C et al. (2016) Neisseria meningitidis Lacking the Major Porins PorA and PorB Is Viable and Modulates Apoptosis and the Oxidative Burst of Neutrophils. J Proteome Res 15:2356-65
Anderson, Mark T; Byerly, Luke; Apicella, Michael A et al. (2016) Seminal Plasma Promotes Neisseria gonorrhoeae Aggregation and Biofilm Formation. J Bacteriol 198:2228-35
Palmer, Guy H; Bankhead, Troy; Seifert, H Steven (2016) Antigenic Variation in Bacterial Pathogens. Microbiol Spectr 4:

Showing the most recent 10 out of 67 publications