SALMONELLA-TYPHIMURIUM INDUCES MEMBRANE RUFFLING BY A GROWTH FACTOR-RECEPTOR-INDEPENDENT MECHANISM

Invasive Salmonella typhimurium induces dramatic actin rearrangements on the membrane surface of mammalian cells as part of its entry mechanism. These changes, which are best characterized as membranous ruffles, closely resemble the membrane changes that occur when a growth factor binds to its receptor. Recently, inhibition of the function of the small GTPases rac and rho in quiescent serum-starved fibroblasts was demonstrated to abolish growth factor-mediated ruffling and stress-fiber formation, respectively. In addition, actin changes induced by the oncogene ras were also shown to be regulated by rac and rho. Because Salmonella-induced actin rearrangements resemble those caused by growth factors, we investigated whether ras, rho, or rac regulates the membrane ruffling elicited by S. typhimurium. Surprisingly, inhibition of the functions of these GTPases had no effect on the ability of invasive S. typhimurium to induce membrane ruffles on a variety of tissue culture cells including Madin-Darby canine kidney cells, Swiss 3T3 fibroblasts, and Hep-2 cells. These results led us to examine the interactions of S. typhimurium with Henle-407 intestinal cells, which lack epidermal growth factor receptor on their membrane surface. We found no difference in the ability of invasive S. typhimurium to induce membrane ruffling and to enter Henle-407 cells with or without the epidermal growth factor receptor on the membrane surface. We, therefore, conclude that invasive S. typhimurium induces membrane ruffling and its own internalization by a rac-independent, growth factor-receptor-independent signaling pathway.