The Locus of Enterocyte Effacement (LEE)-Encoded Regulator Controls Expression of Both LEE- and Non-LEE-Encoded Virulence Factors in Enteropathogenic and Enterohemorrhagic Escherichia coli

doi:10.1128/IAI.68.11.6115-6126.2000

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Infection and Immunity, November 2000, p. 6115-6126, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Locus of Enterocyte Effacement (LEE)-Encoded Regulator Controls Expression of Both LEE- and Non-LEE-Encoded Virulence Factors in Enteropathogenic and Enterohemorrhagic Escherichia coli

Simon J. Elliott,¹ Vanessa Sperandio,¹ Jorge A. Girón,¹^,² Sooan Shin,¹ Jay L. Mellies,¹^,³ Leslie Wainwright,¹^,⁴ Steven W. Hutcheson,¹^,⁵ Timothy K. McDaniel,¹^,⁶ and James B. Kaper¹^,^*

Center for Vaccine Development and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201¹; Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Pue., Mexico²; Department of Biology, Reed College, Portland, Oregon 97202³; Center for Biotechnology, Northwestern University, Evanston, Illinois 60201⁴; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742⁵; and Illumina Inc., San Diego, California 92121⁶

Received 11 April 2000/Returned for modification 26 June 2000/Accepted 7 August 2000

Regulation of virulence gene expression in enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) isincompletely understood. In EPEC, the plasmid-encoded regulatorPer is required for maximal expression of proteins encoded onthe locus of enterocyte effacement (LEE), and a LEE-encoded regulator(Ler) is part of the Per-mediated regulatory cascade upregulatingthe LEE2, LEE3, and LEE4 promoters. We now report that Ler isessential for the expression of multiple LEE-located genes inboth EPEC and EHEC, including those encoding the type III secretionpathway, the secreted Esp proteins, Tir, and intimin. Ler is thereforecentral to the process of attaching and effacing (AE) lesion formation.Ler also regulates the expression of LEE-located genes not requiredfor AE-lesion formation, including rorf2, orf10, rorf10, orf19,and espF, indicating that Ler regulates additional virulence properties.In addition, Ler regulates the expression of proteins encodedoutside the LEE that are not essential for AE lesion formation,including TagA in EHEC and EspC in EPEC. $Delta$ ler mutants of bothEPEC and EHEC show altered adherence to epithelial cells and expressnovel fimbriae. Ler is therefore a global regulator of virulencegene expression in EPEC andEHEC.

^* Corresponding author. Mailing address: Center for Vaccine Development, University of Maryland School of Medicine, 685 W. BaltimoreSt., Baltimore, MD 21201. Phone: (410) 706 2493. Fax: (410) 7060182. E-mail: jkaper{at}umaryland.edu.

Infection and Immunity, November 2000, p. 6115-6126, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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