THE SECRETION OF THE SHIGELLA-FLEXNERI IPA INVASINS IS ACTIVATED BY EPITHELIAL-CELLS AND CONTROLLED BY IPAB AND IPAD

Shigella species are enteropathogens that invade epithelial cells of t he human colon. Entry into epithelial cells is triggered by the IpaB, IpaC and IpaD proteins which are translocated into the medium through the specific Mxi-Spa machinery. In vitro, Shigella cells secrete only a small fraction of the Ipa proteins, the majority of which remains in the cytoplasm. We show here that upon interaction with cultured epith elial cells or in the presence of fetal bovine serum, S.flexneri relea se pre-synthesized Ipa molecules from the cytoplasm into the environme nt, presented that IpaB and IpaD are both blocking secretion through t he Mxi-Spa translocon in the absence of a secretion-inducing signal an d controlling secretion of the Ipa proteins in the presence of a signa l. Subcellular localization and analysis of the molecular interactions of the Ipa proteins indicate that IpaB and IpaD associate transiently in the bacterial envelope. We propose that IpaB and IpaD, by interact ing in the secretion apparatus, modulate secretion.