Magdalene So, PhD, Professor of Immunobiology and Member of the BIO5 Institute, has been awarded a 4-year $1,381,259 grant by the National Institute of Allergy and Infectious Diseases. The project focuses on the Type IV pilus of commensal and pathogenic species of Neisseria, and involves collaborators at Columbia University and City University of New York at Brooklyn. So and her collaborators will determine how the Type IV pilus promotes asymptomatic colonization on the one hand, and symptomatic infection on the other. The project is titled “Type IV pilus as a Switch that determines consequences of Neisseria colonization”.
The Type IV pilus (Tfp) is a virulence factor that mediates initial contact of pathogenic Neisseria with epithelial cells. Subsequently, it 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. Tfp of commensal species of Neisseria also mediates attachment. However, Tfp of commensal and pathogenic Neisseria differ 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 the epithelial cell. This project tests the hypothesis that Tfp is a switch that determines whether Neisseria colonization leads to commensalism (asymptomatic colonization) or pathogenesis. It further tests the hypothesis that 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. So’s lab will identify the transcriptional regulatory networks that control Tfp expression and compare the epithelial cell signal pathways induced by Tfp of commensal and pathogenic Neisseria. Lewis Brown (Columbia) will determine the proteome of epithelial cell cortical plaques induced by commensal and pathogenic Neisseria. Nicolas Biais (CUNY, Brooklyn) will compare the dynamics of Type IV retraction by commensal and pathogenic Neisseria.