Neisseria gonorrhoeae is an obligate human pathogen that causes the common, sexually-transmitted disease, gonorrhea. Both men and women are susceptible to the disease but women often suffer more signiflcant secondary sequelae, including pelvic Inflammatory disease, endometritis and disseminated infections. Host cell invasion is thought to be a key step in gonococcal infection, potentially facilitating immune escape and trans-epithelial migration into deeper tissues. A few published studies have noted that attachment to and invasion of epithelial cells is enhanced in the presence of an utilizable iron source. However, this observation has not been universally appreciated. Iron replete growth conditions exist in environments in which the gonococcus thrives, namely on human mucosal membranes and within the natural transmission fluid, semen. Moreover, iron sources are readily available within the female genital tract during menses, a stage that has been associated with increased risk for ascending gonococcal infections. Thus, iron replete growth condiflons could potentiate invasion, ascension to the upper genital tract and dissemination. In the studies described in this proposal, we intend to define the role that iron plays in gonococcal invasion of epithelial cells. Specifically, the goals of this application are: to determine the mechanism(s) of iron-induced invasion, to define entry pathways that are employed and to ascertain whether this pathway is important for gonococcal virulence in human and murine models of infection.

Public Health Relevance

This application seeks to identify the role that iron plays in contributing to host cell attachment and invasion by Neisseria gonorrhoeae. Iron-regulated invasion pathways will be evaluated for their contributions to gonococcal virulence in human and murine models of infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI031496-23
Application #
8519212
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
23
Fiscal Year
2013
Total Cost
$267,372
Indirect Cost
$40,589
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Kissinger, Patricia J; White, Scott; Manhart, Lisa E et al. (2016) Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis. Sex Transm Dis 43:599-602
Kandler, Justin L; Acevedo, Rosuany Vélez; Dickinson, Mary Kathryne et al. (2016) The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions. Mol Microbiol 102:137-51
Kandler, Justin L; Holley, Concerta L; Reimche, Jennifer L et al. (2016) The MisR Response Regulator Is Necessary for Intrinsic Cationic Antimicrobial Peptide and Aminoglycoside Resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 60:4690-700
Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M et al. (2016) Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women. AIDS Behav :
Scheidell, Joy D; Lejuez, Carl W; Golin, Carol E et al. (2016) Borderline Personality Disorder Symptom Severity and Sexually Transmitted Infection and HIV Risk in African American Incarcerated Men. Sex Transm Dis 43:317-23
Samo, Melissa; Choudhary, Neelima R; Riebe, Kristina J et al. (2016) Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface. Vaccine 34:1193-200
Khan, M R; Golin, C E; Friedman, S R et al. (2015) STI/HIV Sexual Risk Behavior and Prevalent STI Among Incarcerated African American Men in Committed Partnerships: The Significance of Poverty, Mood Disorders, and Substance Use. AIDS Behav 19:1478-90
Unemo, Magnus; Shafer, William M (2015) Future treatment of gonorrhea--novel emerging drugs are essential and in progress? Expert Opin Emerg Drugs 20:357-60
Cash, Devin R; Noinaj, Nicholas; Buchanan, Susan K et al. (2015) Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA Expressed by Neisseria gonorrhoeae. Infect Immun 83:4438-49
Gallo, Maria F; Warner, Lee; Hobbs, Marcia M et al. (2015) Differences in misreporting of sexual behavior over time: implications for HIV trials. Sex Transm Dis 42:160-1

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