Neisseria gonorrhoeae (Gc) is an obligate human pathogen that is the causative agent of the sexually transmitted disease gonorrhea. All freshly isolated Gc express pili on their cell surfaces; and the expression of the pilus is required for infection in human volunteers. The most unique characteristic of Gc pili is the large number of possible pilus antigenic types that a single organism can produce. This antigenic variation process occurs by recombination between one of several silent pilin gene copies and the singular expressed gene (that encodes the major subunit of the pilus, pilin), resulting in multiple sequence changes in the expressed gene and protein. This system of pilin antigenic variation provides a large mosaic of antigenic types in a Gc population, and allows continual reinfection of the high risk portion of the human population that transmits Gc into the general population. Much of our understanding about the mechanisms that produce and control pilin antigenic variation has been obtained by determining the types of sequence changes that occur when an antigenic switch occurs. For each antigenic switch, a portion of one of 19 silent pilin gene copies is transferred to the pilE locus in a nonreciprocal fashion. The investigators have isolated a number of cis and trans-acting mutation that disrupt the process of pilin antigenic variation and predict molecular mechanisms that promote the high frequency transfer of variable pilin sequences. They will continue to isolate and characterize genes, proteins, and cis-acting DNA sequences that are required for pilin antigenic variation to test between different hypotheses about how pilin antigenic variation is mediated. They will also explore the possibility that pilin antigenic variation is regulated during human infection. Through these investigations, this project will continue to define the molecular mechanism used to allow these high frequency recombination reactions that are of critical importance to the pathogenesis of gonorrhea.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI033493-05
Application #
2467897
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1994-05-01
Project End
2003-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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 :
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
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
Rotman, Ella; Seifert, H Steven (2015) Neisseria gonorrhoeae MutS affects pilin antigenic variation through mismatch correction and not by pilE guanine quartet binding. J Bacteriol 197:1828-38
Anderson, Mark T; Seifert, H Steven (2013) Phase variation leads to the misidentification of a Neisseria gonorrhoeae virulence gene. PLoS One 8:e72183
Vink, Cornelis; Rudenko, Gloria; Seifert, H Steven (2012) Microbial antigenic variation mediated by homologous DNA recombination. FEMS Microbiol Rev 36:917-48
Duffin, Paul M; Seifert, H Steven (2012) Genetic transformation of Neisseria gonorrhoeae shows a strand preference. FEMS Microbiol Lett 334:44-8
Schook, Paul O P; Stohl, Elizabeth A; Criss, Alison K et al. (2011) The DNA-binding activity of the Neisseria gonorrhoeae LexA orthologue NG1427 is modulated by oxidation. Mol Microbiol 79:846-60
Stohl, Elizabeth A; Gruenig, Marielle C; Cox, Michael M et al. (2011) Purification and characterization of the RecA protein from Neisseria gonorrhoeae. PLoS One 6:e17101
Duffin, Paul M; Seifert, H Steven (2009) ksgA mutations confer resistance to kasugamycin in Neisseria gonorrhoeae. Int J Antimicrob Agents 33:321-7

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