PRIMARY FACULTY
Ann Jerse, Ph.D.
Professor
Microbiology & Immunology
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-9629
Fax: 301-295-1996
ajerse@usuhs.mil
Pathogenesis of Neisseria gonorrhoeae and development of gonorrhea vaccines
Colonization of the female genital tract by Neisseria gonorrhoeae can be asymptomatic or cause acute inflammation of the cervix. This pathogen frequently ascends to the upper reproductive tract resulting in scarring of the fallopian tubes and pelvic inflammatory disease. To provide an in vivo system for studying how N. gonorrhoeae adapts to the female host and to facilitate pre-clinical testing of vaccines and other prophylactic agents, we developed a female mouse model of gonococcal genital tract infection. This system has been useful for studying many aspects of gonococcal infection, including evasion of PMN killing through the expression of anti-oxidant factors and surface sialylation, evasion of host antimicrobial substances that are expelled through the MtrC-MtrD-MtrE active efflux pump system, interactions with commensal flora, and the host response to infection. Phase variation of gonococcal surface proteins called the opacity (Opa) proteins also occurs during infection, and we have shown that gonadal steroids play in selection of certain Opa variants. A second aspect of our research program is the
development of a gonorrhea vaccine. In addition to testing purified outer membrane proteins, we are developing vaccine antigens that mimic surface-exposed loops of outer membrane proteins known to play a role in colonization or protection of gonococci from innate defenses.
Selected Pathogenesis Studies
- Simms, A.N. and A.E. Jerse. 2006. In vivo selection for Neisseria gonorrhoeae opacity protein expression in the absence of human carcinoembryonic antigen cell adhesion molecules. Infect Immun. 74(5):2965-74.
- Wu, H. and A.E. Jerse. 2006. Alpha-2,3-sialyltransferase enhances Neisseria gonorrhoeae survival during experimental murine genital tract infection. Infect Immun. 74(7):4094-103.
- Soler-Garcia A.A. and A.E. Jerse. 2007. Neisseria gonorrhoeae catalase is not required for experimental genital tract infection despite the induction of a localized neutrophil response. Infect. Immun. 75:2225-2233.
- Exley RM, Wu H, Shaw J, Schneider MC, Smith H, Jerse AE, Tang CM. 2007. Lactate acquisition promotes successful colonization of the murine genital tract by Neisseria gonorrhoeae. Infect Immun. 75(3):1318-24.
- Warner DM, Folster JP, Shafer WM, Jerse AE.. 2007. Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J Infect Dis. 196(12):1804-12.
- Garvin LE, Bash MC, Keys C, Warner DM, Ram S, Shafer WM, Jerse AE.. 2008. Phenotypic and Genotypic Analyses of Neisseria gonorrhoeae Isolates that Express Frequently Recovered PorB PIA Variable Region (VR) Types Suggest Certain P1A Porin Sequences Confer a Selective Advantage for Urogenital Tract Infection. Infect Immun. 76:3700-3709.
- Song W., Condron S., Mocca B.T., Veit S.J., Hill D., Abbas A., and A.E. Jerse. 2008. Local and humoral responses against primary and repeat Neisseria gonorrhoeae genital tract infections of 17-ß-estradiol-treated mice. Vaccine 26:5741-5751.
- Warner D.J., W.M. Shafer, and A.E. Jerse. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol. Micro. 70:462-478.
- Wu H., Soler-Garcia A.A., and A.E. Jerse. 2009. A strain-specific catalase mutation and mutation of the metal-binding transporter gene mntC attenuate Neisseria gonorrhoeae in vivo, but not by increasing susceptibility to oxidative killing by phagocytes Infect. Immun. 77:1091-1102
Pre-clinical testing of microbicides, probiotics, and vaccines
- Plante, M. , A.E. Jerse, J. Hamel, F. Coutre, C.R. Rioux, B.R. Brodeur, and D. Martin. 2000. Intranasal immunization with gonococcal outer membrane preparations reduces the duration of vaginal colonization of mice by Neisseria gonorrhoeae. J. Infect. Dis. 182:848-855.
- Spencer, S.E., Valentin-Bon, I.E., Whaley, K., and A.E. Jerse. 2004. Inhibition of Neisseria gonorrhoeae genital tract infection by leading candidate topical microbicides in a mouse model. J. Infect. Dis. 189:410-419.
- Muench D.F., Kuch D.J., Wu H., Begum A.A., Veit S.J., Pelletier M. E., Soler-Garcia A.A., and A.E. Jerse. 2009. H2O2-producing lactobacilli inhibit gonococci in vitro but not during experimental genital tract infection. J. Infect. Dis. 199:1369-78.
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