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Journal of Bacteriology, January 2005, p. 349-357, Vol. 187, No. 1
0021-9193/05/$08.00+0     doi:10.1128/JB.187.1.349-357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Ler Is a Negative Autoregulator of the LEE1 Operon in Enteropathogenic Escherichia coli

Tatiana Berdichevsky, Devorah Friedberg, Chen Nadler, Assaf Rokney, Amos Oppenheim, and Ilan Rosenshine*

Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel

Received 21 June 2004/ Accepted 6 September 2004

Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. Essential for colonization of the host intestine is the LEE pathogenicity island, which comprises a cluster of operons encoding a type III secretion system and related proteins. The LEE1 operon encodes Ler, which positively regulates many EPEC virulence genes in the LEE region and elsewhere in the chromosome. We found that Ler acts as a specific autorepressor of LEE1 transcription. We further show that Ler specifically binds upstream of the LEE1 operon in vivo and in vitro. A comparison of the Ler affinities to different DNA regions suggests that the autoregulation mechanism limits the steady-state level of Ler to concentrations that are just sufficient for activation of the LEE2 and LEE3 promoters and probably other LEE promoters. This mechanism may reflect the need of EPEC to balance maximizing the colonization efficiency by increasing the expression of the virulence genes and minimizing the immune response of the host by limiting their expression. In addition, we found that the autoregulation mechanism reduces the cell-to-cell variability in the levels of LEE1 expression. Our findings point to a new negative regulatory circuit that suppresses the noise and optimizes the expression levels of ler and other LEE1 genes.


* Corresponding author. Mailing address: Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, POB 12272, Jerusalem 91120, Israel. Phone: 972 2 6758754. Fax: 972 2 6757308. E-mail: ilanro{at}cc.huji.ac.il


Journal of Bacteriology, January 2005, p. 349-357, Vol. 187, No. 1
0021-9193/05/$08.00+0     doi:10.1128/JB.187.1.349-357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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