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Journal of Bacteriology, October 2003, p. 6032-6041, Vol. 185, No. 20
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.20.6032-6041.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Iron-Responsive Regulator Fur Is Transcriptionally Autoregulated and Not Essential in Neisseria meningitidis

Isabel Delany,1 Raffaele Ieva,1 Cristina Alaimo,1,{dagger} Rino Rappuoli,1 and Vincenzo Scarlato1,2*

Biochemistry and Molecular Biology Unit, IRIS, Chiron S.r.l., 53100 Siena,1 Department of Biology, University of Bologna, 40126 Bologna, Italy2

Received 21 April 2003/ Accepted 28 July 2003

Fur is a well-known iron-responsive repressor of gene transcription, which is used by many bacteria to respond to the low-iron environment that pathogens encounter during infection. The fur gene in Neisseria meningitidis has been described as an essential gene that may regulate a broad array of genes. We succeeded in obtaining an N. meningitidis mutant with the fur gene knocked out and used it to undertake studies of fur-mediated iron regulation. We show that expression of both Fur and the transferrin binding protein Tbp2 is iron regulated and demonstrate that this regulation is Fur mediated for the Tbp2 protein. Footprinting analysis revealed that Fur binds to two distinct sites upstream of its coding region with different affinities and that these binding sites overlap two promoters that differentially control transcription of the fur gene in response to iron. The presence of two independently regulated fur promoters may allow meningococcus to fine-tune expression of this regulator controlling iron homeostasis, possibly during infection.

* Corresponding author. Mailing address: Biochemistry and Molecular Biology Unit, IRIS, Chiron S.r.l., Via Fiorentina 1, 53100 Siena, Italy. Phone: 39 0577 243565. Fax: 39 0577 243564. E-mail: enzo_scarlato{at}chiron.it.

{dagger} Present address: Institut für Mikrobiologie ETH, CH-8092 Zürich, Switzerland.

Journal of Bacteriology, October 2003, p. 6032-6041, Vol. 185, No. 20
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.20.6032-6041.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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