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Infection and Immunity, August 2006, p. 4462-4473, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00575-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mutational Analysis of RetS, an Unusual Sensor Kinase-Response Regulator Hybrid Required for Pseudomonas aeruginosa Virulence{dagger}

Michelle A. Laskowski1,2,3 and Barbara I. Kazmierczak2,3*

Program in Microbiology,1 Department of Internal Medicine,2 Section of Microbial Pathogenesis, Yale University School of Medicine, P.O. Box 208022, New Haven, Connecticut 06520-80223

Received 6 April 2006/ Returned for modification 17 May 2006/ Accepted 24 May 2006

Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in a wide range of hosts. Expression of the type III secretion system (T3SS) proteins is correlated with virulence in models of acute infection, while downregulation of the T3SS and upregulation of genes important for biofilm formation are observed during chronic infections. RetS, a hybrid sensor kinase-response regulator protein of P. aeruginosa, plays a key role in the reciprocal regulation of virulence factors required for acute versus chronic infection and is postulated to act in concert with two other sensor kinase-response regulator hybrids, GacS and LadS. This work examines the roles of the putative sensing and signal transduction domains of RetS in induction of the T3SS in vitro and in a murine model of acute pneumonia. We identify distinct signaling roles for the tandem receiver domains of RetS and present evidence suggesting that RetS may serve as a substrate for another sensor kinase. Phenotypes associated with RetS alleles lacking periplasmic and/or transmembrane domains further indicate that the periplasmic domain of RetS may transmit a signal that inhibits RetS activity during acute infections.


* Corresponding author. Mailing address: Yale University School of Medicine, 333 Cedar Street, P.O. Box 208022, New Haven, CT 06520-8022. Phone: (203) 737-5062. Fax: (203) 785-3864. E-mail: barbara.kazmierczak{at}yale.edu.

Editor: J. T. Barbieri

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.


Infection and Immunity, August 2006, p. 4462-4473, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00575-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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