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Journal of Bacteriology, April 2003, p. 2618-2627, Vol. 185, No. 8
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.8.2618-2627.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The REP2 Repeats of the Genome of Neisseria meningitidis Are Associated with Genes Coordinately Regulated during Bacterial Cell Interaction

Sandrine Morelle, Etienne Carbonnelle, and Xavier Nassif*

INSERM U570, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, Paris, France

Received 23 September 2002/ Accepted 8 January 2003

Interaction with host cells is essential in meningococcal pathogenesis especially at the blood-brain barrier. This step is likely to involve a common regulatory pathway allowing coordinate regulation of genes necessary for the interaction with endothelial cells. The analysis of the genomic sequence of Neisseria meningitidis Z2491 revealed the presence of many repeats. One of these, designated REP2, contains a -24/-12 type promoter and a ribosome binding site 5 to 13 bp before an ATG. In addition most of these REP2 sequences are located immediately upstream of an ORF. Among these REP2-associated genes are pilC1 and crgA, described as being involved in steps essential for the interaction of N. meningitidis with host cells. Furthermore, the REP2 sequences located upstream of pilC1 and crgA correspond to the previously identified promoters known to be induced during the initial localized adhesion of N. meningitidis with human cells. This characteristic led us to hypothesize that at least some of the REP2-associated genes were upregulated under the same circumstances as pilC1 and crgA. Quantitative PCR in real time demonstrated that the expression of 14 out of 16 REP2-associated genes were upregulated during the initial localized adhesion of N. meningitidis. Taken together, these data suggest that these repeats control a set of genes necessary for the efficient interaction of this pathogen with host cells. Subsequent mutational analysis was performed to address the role of these genes during meningococcus-cell interaction.

* Corresponding author. Mailing address: INSERM U570, Laboratoire de Microbiologie, Faculté de Médecine Necker-Enfants Malades, 156, rue de Vaugirard, 75015 Paris, France. Phone: 33-140615678. Fax: 33-4061535592. E-mail: nassif{at}necker.fr.

Journal of Bacteriology, April 2003, p. 2618-2627, Vol. 185, No. 8
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.8.2618-2627.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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