Type IV pilus as a switch that determines consequences of Neisseria colonization

Project: Research project

Description

DESCRIPTION (provided by applicant): The Type IV pilus (Tfp) is a virulence factor that mediates the initial contact of pathogenic Neisseria with epithelial cells. It subsequently activates signaling pathways that modulate cellular responses to infection. Attachment is mediated by static Tfp fibers. Signaling requires physical force exerted on the colonized cell by retracting fibers. Our preliminary findings indicate Tfp of commensal Neisseria also mediates attachment. However, the biology of commensal and pathogenic Neisseria Tfp differs in two major respects. 1) Tfp genes encoding the attachment and retraction components are under different transcriptional regulation. 2) Tfp retraction activates different signaling cascades in te epithelial cell. We hypothesize Tfp is a switch that determines whether Neisseria colonization leads to commensalism (asymptomatic colonization) or pathogenesis. This is analogous to a railroad switch at a junction that directs a train (bacterium) down tracks leading to different destinations (commensalism or pathogenesis). We further hypothesize the Tfp switching mechanism consists of two critical components: transcriptional regulation of its machinery genes, and its epithelial cell signaling activities. Transcriptional regulation determines when and
where Tfp-mediated attachment and retraction occur. The types of signaling cascades activated in the host cell determine the outcome of colonization. We propose two Aims to test this hypothesis.
StatusFinished
Effective start/end date8/8/137/31/18

Funding

  • National Institutes of Health: $416,433.00
  • National Institutes of Health: $570,653.00
  • National Institutes of Health: $516,463.00
  • National Institutes of Health: $416,433.00

Fingerprint

Neisseria
Symbiosis
Epithelial Cells
Railroads
Virulence Factors
Genes
Bacteria
Infection

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)