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Infection and Immunity, July 2007, p. 3282-3289, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00045-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The HlyU Protein Is a Positive Regulator of rtxA1, a Gene Responsible for Cytotoxicity and Virulence in the Human Pathogen Vibrio vulnificus{triangledown} ,{dagger}

Moqing Liu, Alejandro F. Alice, Hiroaki Naka, and Jorge H. Crosa*

Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon

Received 9 January 2007/ Returned for modification 26 February 2007/ Accepted 9 April 2007

Vibrio vulnificus is an opportunistic human pathogen that preferentially infects compromised iron-overloaded patients, causing a fatal primary septicemia with very rapid progress, resulting in a high mortality rate. In this study we determined that the HlyU protein, a virulence factor in V. vulnificus CMCP6, up-regulates the expression of VV20479, a homologue of the Vibrio cholerae RTX (repeats in toxin) toxin gene that we named rtxA1. This gene is part of an operon together with two other open reading frames, VV20481 and VV20480, that encode two predicted proteins, a peptide chain release factor 1 and a hemolysin acyltransferase, respectively. A mutation in rtxA1 not only contributes to the loss of cytotoxic activity but also results in a decrease in virulence, whereas a deletion of VV20481 and VV20480 causes a slight decrease in virulence but with no effect in cytotoxicity. Activation of the expression of the rtxA1 operon by HlyU occurs at the transcription initiation level by binding of the HlyU protein to a region upstream of this operon.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239. Phone: (503) 494-7583. Fax: (503) 494-6862. E-mail: crosajor{at}ohsu.edu

{triangledown} Published ahead of print on 16 April 2007.

{dagger} Supplemental material for this article is available at http://iai.asm.org/.

Editor: A. D. O'Brien

Infection and Immunity, July 2007, p. 3282-3289, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00045-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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