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 #
5U19AI031496-22
Application #
8381153
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
22
Fiscal Year
2012
Total Cost
$284,153
Indirect Cost
$48,440
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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