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Infection and Immunity, June 2002, p. 2915-2925, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.2915-2925.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of the Overlapping pic/set Locus in Shigella flexneri and Enteroaggregative Escherichia coli

Martin Behrens,,{dagger} Jalaluddin Sheikh, and James P. Nataro*

Center for Vaccine Development, Departments of Pediatrics, Medicine, and Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201

Received 20 September 2001/ Returned for modification 6 December 2001/ Accepted 14 February 2002

Most strains of Shigella flexneri 2a and enteroaggregative Escherichia coli carry a highly conserved chromosomal locus which encodes a 109-kDa secreted mucinase (called Pic) and, on the opposite strand in overlapping fashion, an oligomeric enterotoxin called ShET1, encoded by the setA and setB genes. Here, we characterize the genetic regulation of these overlapping genes. Our data suggest that pic and the setBA loci are transcribed as complementary 4-kb mRNA species. The major pic promoter is maximally activated at 37°C in exponential growth phase. Our data suggest that the setB gene is transcribed from a promoter which lies more than 1.5 kb upstream of the setB structural gene; setA may be transcribed via readthrough of the setB transcript and possibly by its own promoter. The long leader of the setB gene provides a strong silencing effect on setB transcription. The signals which provide relief from setB silencing are not clear, but significant induction is observed in a continuous anaerobic culture of human fecal bacteria, suggesting that some complex characteristics of the human intestine act to lift repression of setB expression. Our studies provide the first insights into the mechanisms affecting expression of this unusual virulence locus.

* Corresponding author. Mailing address: 685 W. Baltimore St., Baltimore MD 21201. Phone: (410) 706-5328. Fax: (410) 706-6205. E-mail: jnataro{at}medicine.umaryland.edu.

Editor: D. L. Burns

{dagger} Present address: Limetec Biotechnologies GmbH, 16321 Bernau bei Berlin, Germany.

Infection and Immunity, June 2002, p. 2915-2925, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.2915-2925.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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