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Infection and Immunity, December 2005, p. 7938-7945, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7938-7945.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Leucine-Rich Motif Targets Pseudomonas aeruginosa ExoS within Mammalian Cells

Yue Zhang and Joseph T. Barbieri*

Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226

Received 26 May 2005/ Returned for modification 12 July 2005/ Accepted 30 August 2005

Type III cytotoxins contribute to the ability of bacterial pathogens to subvert the host innate immune system. ExoS (453 amino acids) is a bifunctional type III cytotoxin produced by Pseudomonas aeruginosa. Residues 96 to 232 comprise a Rho GTPase activating protein domain, while residues 233 to 453 comprise a 14-3-3-dependent ADP-ribosyltransferase domain. An N-terminal domain (termed the membrane localization domain [MLD]) targets ExoS to the Golgi-endoplasmic reticulum (Golgi-ER) of mammalian cells. This study identifies an amino acid motif that is responsible for the membrane binding properties of the MLD. Deletion mapping showed that the MLD included a symmetrical leucine-rich motif within residues 51 to 77 of ExoS. The terminal dileucines and internal leucines and an isoleucine within the MLD, but not charged or other hydrophobic residues, targeted a reporter protein to the Golgi-ER region of HeLa cells. Mutations of the leucines within the MLD did not affect type III secretion or translocation into HeLa cells but limited the ability of ExoS to ADP-ribosylate Ras GTPases. Mutations of charged residues within the MLD did not affect type III secretion, delivery into HeLa cells, or the ability of ExoS to ADP-ribosylate Ras GTPases. The organization of the leucines within the MLD of ExoS is different from that of previously described leucine-rich motifs but is present in several other bacterial proteins. This implies a role for intracellular targeting in the efficient targeting of mammalian cells by type III cytotoxins.

* Corresponding author. Mailing address: Medical College of Wisconsin, Microbiology and Molecular Genetics, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Phone: (414) 456-8412. Fax: (414) 456-6535. E-mail: jtb01{at}mcw.edu.

Editor: J. B. Bliska

Infection and Immunity, December 2005, p. 7938-7945, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7938-7945.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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