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Journal of Bacteriology, October 2005, p. 7009-7017, Vol. 187, No. 20
0021-9193/05/$08.00+0     doi:10.1128/JB.187.20.7009-7017.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The lrp Gene and Its Role in Type I Fimbriation in Citrobacter rodentium

Angela Cordone,^1,¶ Emilia M. F. Mauriello,^1,¶ Derek J. Pickard,² Gordon Dougan,² Maurilio De Felice,¹ and Ezio Ricca^1*

Dipartimento di Biologia Strutturale e Funzionale, Università Federico II, Naples, Italy,¹ The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom²

Received 11 April 2005/ Accepted 23 June 2005

Citrobacter rodentium is a murine pathogen that is now widely used as an in vivo model for gastrointestinal infections due to its similarities with human enteropathogens, such as the possession of a locus for enterocyte effacement (the LEE island). We studied the lrp gene of C. rodentium and found that it encodes a product highly similar to members of the Lrp (leucine-responsive regulatory protein) family of transcriptional regulators, able to recognize leucine as an effector and to repress the expression of its own structural gene. In enterobacteria, Lrp is a global regulator of gene expression, as it controls a large variety of genes, including those coding for cell appendages and other potential virulence factors. Based on the well-established role of Lrp on the expression of pilus genes in Escherichia coli, we also studied the role of Lrp in controlling the formation of the type I pilus in C. rodentium. Type I pili, produced by the fim system, are virulence factors of uropathogens, involved in mediating bacterial adhesion to bladder epithelial cells. Yeast agglutination assays showed that Lrp is needed for type I pilus formation and real-time PCR experiments indicated that Lrp has a strong leucine-mediated effect on the expression of the fimAICDFGH operon. Mutant studies indicated that this positive action is exerted mainly through a positive control of Lrp on the phase variation mechanism that regulates fimAICDFGH expression. A quantitative analysis of its expression suggested that this operon may also be negatively regulated at the level of transcription.

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* Corresponding author. Mailing address: Dipartimento di Biologia Strutturale e Funzionale, Università Federico II, via Cinthia, Complesso Monte S. Angelo, 80126, Naples, Italy. Phone: 39-081-2534636. Fax: 39-081-5514437. E-mail: ericca{at}unina.it.

^¶ These two authors contributed equally to the work.

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Journal of Bacteriology, October 2005, p. 7009-7017, Vol. 187, No. 20
0021-9193/05/$08.00+0     doi:10.1128/JB.187.20.7009-7017.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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