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Hank S. Seifert, PhDProfessor
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Neisseria gonorrhoeae is the sole causative agent of the sexually transmitted disease gonorrhea. The gonococcal pilus is a major virulence factor that mediates the initial interactions of the bacterium with its human host. The pilus functions in enhancing adherence of the bacterium to host cells, locomotion of the bacterium, and genetic transfer between bacteria. The pilus structural protein, pilin, undergoes high frequency antigenic variation to assist in evasion of the host immune responses. We are defining the molecular mechanisms used to produce pilus antigenic variation by identifying the gene products required, their biochemical activities, and the DNA sequences used in this homologous recombination process. These studies have allowed us to develop novel models for gene conversion and uncover new mechanisms by which recombination can occur. The studies of the recombination mechanisms underlying antigenic variation intersect with our investigation into general DNA recombination and DNA repair capabilities of this organism -- specifically how it protects from the innate immune response mediated by neutrophils. In addition, how the pilus is expressed on the bacterial cell surface and mediates its functions is also under investigation.
Criss, AK & Seifert, HS (2006) Gonococci exit apically and basally from polarized epithelial cells and exhibit dynamic changes in type IV piliation. Cell Micro. 8: 1430-1443.
Sechman, EV, Kline KA & Seifert, HS (2006) Loss of both Holliday Junction branch migration pathways of Neisseria gonorrhoeae is synthetically lethal in the presence of pilin antigenic variation. Mol Micro. 61 185-193.
Tobiason, D & Seifert HS (2006) The diplococcus, Neisseria gonorrhoeae, is polyploid. PLoS Biology 4: 1069-1078. [Research Highlight: Nature 441:1030-31].
Lusetti, SL, Hobbs, MD, Stohl, EA, Chitteni-Pattu, S, Inman, RB, Seifert, HS, & Cox, MM. (2006) The RecF protein antagonizes RecX function via direct interaction. Mol. Cell. 21: 41-50.
Stohl, EA, Criss, AK & Seifert, HS (2005) The transcriptome response of Neisseria gonorrhoeae to hydrogen peroxide reveals genes with previously uncharacterized roles in oxidative damage protection. Mol Microbiol. 58: 520-533.
Criss, AK., Kline, K.A. & Seifert, HS. (2005) The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae. Mol Microbiol. 58: 510-519.
Zhao, S#., Tobiason, DM#., Hu M., Seifert, HS, & RA. Nicholas. (2005) The penC mutation conferring antibiotic resistance in Neisseria gonorrhoeae arises from a mutation in the PilQ secretin that interferes with multimer assembly and prevents antibiotic influx. Mol. Microbiol. 57: 1238-1251. (#.Co-first authors).
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View Publications by Hank Seifert listed in the National Library of Medicine (PubMed). |
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