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Infection and Immunity, June 2006, p. 3334-3341, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.00090-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcriptional Induction of the Pseudomonas aeruginosa Type III Secretion System by Low Ca2+ and Host Cell Contact Proceeds through Two Distinct Signaling Pathways

Nandini Dasgupta,1 Alix Ashare,2 Gary W. Hunninghake,2,3 and Timothy L. Yahr1*

Departments of Microbiology,1 Internal Medicine, University of Iowa, Iowa City, Iowa 52242,2 the Veterans' Administration Medical Center, Iowa City, Iowa3

Received 17 January 2006/ Returned for modification 8 February 2006/ Accepted 1 April 2006

The opportunistic pathogen Pseudomonas aeruginosa utilizes a type III secretion system (T3SS) to intoxicate eukaryotic host cells. Transcription of the T3SS is induced under calcium-limited growth conditions or following intimate contact of P. aeruginosa with host cells. In the present study, we demonstrate that expression of the T3SS is controlled by two distinct regulatory mechanisms and that these mechanisms are differentially activated in a host cell-dependent manner. The first mechanism is dependent upon ExsC, a regulatory protein that couples transcription of the T3SS to the activity of the type III secretion machinery. ExsC is essential for induction of the T3SS under low-calcium-growth conditions and for T3SS-dependent cytotoxicity towards social amoebae, insect cells, and erythrocytes. The second regulatory mechanism functions independently of ExsC and is sufficient to elicit T3SS-dependent cytotoxicity towards certain types of mammalian cells. Although this second pathway (ExsC independent) is sufficient, an exsC mutant demonstrates a lag in the induction of cytotoxicity towards Chinese hamster ovary cells and is attenuated for virulence in a mouse pneumonia model. We propose that the ExsC-dependent pathway is required for full cytotoxicity towards all host cell types tested whereas the ExsC-independent pathway may represent an adaptation that allows P. aeruginosa to increase expression of the T3SS in response to specific types of mammalian cells.


* Corresponding author. Mailing address: Department of Microbiology, 540B Eckstein Medical Research Building, University of Iowa, Iowa City, IA 52242-1101. Phone: (319) 335-9688. Fax: (319) 335-8228. E-mail: timothy-yahr{at}uiowa.edu.

Editor: J. T. Barbieri


Infection and Immunity, June 2006, p. 3334-3341, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.00090-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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