Type IV pilus retraction is required for Neisseria musculi colonization and persistence in a natural mouse model of infection

Retraction of the pathogenic Neisseria Type IV pilus (Tfp) requires PilT, the primary retraction motor, and its paralogs PilU and PilT2. The importance of Tfp retraction for natural infection is unknown. Using our natural animal model of Neisseria-host interaction, we have examined the role of these proteins in the ability of commensal Neisseria musculi (Nmus) to colonize and persist in its native host, the mouse. We report that Nmus Delta pilT cannot colonize mice; Delta pilU and Delta pilT2 can colonize and persist in mice, but in lower numbers. Microcolonies formed by Delta pilT, Delta pilTU, and pilT(L201C), expressing PilT with a point mutation in its ATP hydrolysis domain, are sensitive to removal by fluid shear forces. Thus, PilT promotes Nmus colonization while PilU and PilT2 influence persistence. We present a non-exclusive model for how these Tfp retraction motor proteins contribute to Nmus persistent colonization. Our findings have implications for the roles of these motor proteins in mediating interactions of human-adapted pathogenic and commensal Neisseria with their human host.