Intracellular Life Cycle of N-gonorrhoeae
Oregon Health & Science University, Portland OR
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Abstract
DESCRIPTION (provided by applicant): Neisseria gonorrhoeae (GC) is a human pathogen that causes a sexually transmitted disease with significant morbidity. GC colonizes and invades nonciliated mucosal epithelial cells. It replicates within these cells then traffics to, and exits from, the basolateral cellular membrane. At this site, GC elicits the inflammatory responses that are characteristic of a mucosal gonorrhea infection. Although a significant part of the GC lifecycle involves bacterial survival and replication within cells, little is known about its intracellular environment. GC induces major signal transduction pathways in the host cell early during attachment. A number of virulence factors trigger and enhance these events, including the type IV pilus (Tfp) and the IgA protease (IgAP). I propose to test the hypothesis that the early signaling events triggered by Tfp and IgAP influence the immediate intracellular environment of GC and promote its intracellular survival. A better understanding of the GC intracellular environment will yield valuable information on the lifecycle of this important pathogen. As Tfp and IgAP are expressed by many other bacterial pathogens, our study may shed light on other bacterial survival mechanisms. It is likely to also identify novel drug targets. Finally, the protocols developed in this project will be a useful tool to explore the intracellular environments of other pathogens.
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