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Infection and Immunity, August 2006, p. 4391-4400, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00440-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

IpaD Localizes to the Tip of the Type III Secretion System Needle of Shigella flexneri

Departments of Molecular Biosciences,¹ Pharmaceutical Chemistry,² and KU Center for Research, Inc., University of Kansas, Lawrence, Kansas 66045,³ Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910⁴

Received 17 March 2006/ Returned for modification 1 May 2006/ Accepted 19 May 2006

Shigella flexneri, the causative agent of shigellosis, is a gram-negative bacterial pathogen that initiates infection by invading cells within the colonic epithelium. Contact with host cell surfaces induces a rapid burst of protein secretion via the Shigella type III secretion system (TTSS). The first proteins secreted are IpaD, IpaB, and IpaC, with IpaB and IpaC being inserted into the host cell membrane to form a pore for translocating late effectors into the target cell cytoplasm. The resulting pathogen-host cross talk results in localized actin polymerization, membrane ruffling, and, ultimately, pathogen entry. IpaD is essential for host cell invasion, but its role in this process is just now coming to light. IpaD is a multifunctional protein that controls the secretion and presentation of IpaB and IpaC at the pathogen-host interface. We show here that antibodies recognizing the surface-exposed N terminus of IpaD neutralize Shigella's ability to promote pore formation in erythrocyte membranes. We further show that MxiH and IpaD colocalize on the bacterial surface. When TTSS needles were sheared from the Shigella surface, IpaD was found at only the needle tips. Consistent with this, IpaD localized to the exposed tips of needles that were still attached to the bacterium. Molecular analyses then showed that the IpaD C terminus is required for this surface localization and function. Furthermore, mutations that prevent IpaD surface localization also eliminate all IpaD-related functions. Thus, this study demonstrates that IpaD localizes to the TTSA needle tip, where it functions to control the secretion and proper insertion of translocators into host cell membranes.

Editor: J. T. Barbieri

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