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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) is incompletely understood. In EPEC, the
plasmid-encoded regulator Per is required for maximal expression
of proteins encoded on the locus of enterocyte effacement (LEE), and a
LEE-encoded regulator (Ler) is part of the Per-mediated regulatory
cascade upregulating the LEE2, LEE3, and
LEE4 promoters. We now report that Ler is essential for the
expression of multiple LEE-located genes in both EPEC and EHEC,
including those encoding the type III secretion pathway, the secreted
Esp proteins, Tir, and intimin. Ler is therefore central to the process
of attaching and effacing (AE) lesion formation. Ler also regulates
the expression of LEE-located genes not required for 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 encoded outside the LEE that are
not essential for AE lesion formation, including TagA in EHEC and EspC
in EPEC.
ler mutants of both EPEC and EHEC show altered
adherence to epithelial cells and express novel fimbriae. Ler is
therefore a global regulator of virulence gene expression in EPEC and EHEC.
*
Corresponding author. Mailing address: Center for
Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD 21201. Phone: (410) 706 2493. Fax: (410)
706 0182. 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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