Defense Date

2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Microbiology & Immunology

First Advisor

Cynthia Cornelissen

Abstract

Iron is an essential nutrient that is sequestered by iron-binding proteins in the human host resulting in a hostile environment for microbes. Neisseria gonorrhoeae, however, can utilize numerous iron-binding proteins such as transferrin and lactoferrin to acquire this nutrient. During initial infection, gonococci have access to transferrin and lactoferrin present in semen and vaginal fluids, as well as to hemoglobin present in blood during menses or disseminated infections. Consequently, the gonococcus likely encounters conditions of high iron at some stages in the course of natural infection. Potential contributions of iron to gonococcal invasion have however been largely over looked in the field as most studies investigating invasion represent iron depleted environments. Considering the link between menses in women and ascending gonococcal infections, we hypothesized that high iron concentrations present at this time triggers the induction of membrane proteins that enhance gonococcal pathogenesis. Here, we report the gonococcal iron-induced surface proteome and show evidence of post-translational modification of many of these proteins. We also present evidence of an iron enhanced, Opa-independent invasion mechanism. Finally, we investigated the role of NspA, TdfJ and NGO1063 on Opa-independent iron induced invasion. Our studies underscore the importance of investigating the effect of iron on gonococcal host cell interactions. Given the potential clinical relevancy of this phenomenon, data from our studies represent a solid framework for further investigation of gonococcal pathogenesis.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-2014

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