Abstract

Intimate cell contact and subsequent type three secretion system-dependent cell invasion are key steps in host colonization of Salmonella. Adhesion to complex glycostructures at the apical membrane of polarized cells is mediated by the giant adhesin SiiE. This protein is secreted by a type 1 secretion system (T1SS) and needs to be retained at the bacterial surface to exert its adhesive function. Here, we show that SiiE surface expression was linked to the presence of L-aspartate sensed by the Salmonella-specific methyl-accepting chemotaxis protein CheM. Bacteria lacking CheM were attenuated for invasion of polarized cells, whereas increased invasion was seen with Salmonella exposed to the non-metabolizable aspartate analog -methyl-D, L-aspartate (MeAsp). While components of the chemotaxis phosphorelay or functional flagella were dispensable for the increased invasion, CheM directly interacted with proteins associated with the SiiE T1SS arguing for a novel non-canonical signaling mechanism. As a result, CheM attractant signaling caused a shift from secreted to surface-retained and adhesion-competent SiiE. Thus, CheM controls the virulence function of SiiE in a precise spatio-temporal fashion depending on the host micro-milieu.