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Journal of Bacteriology, May 2005, p. 3421-3430, Vol. 187, No. 10
0021-9193/05/$08.00+0     doi:10.1128/JB.187.10.3421-3430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CrgA Is an Inducible LysR-Type Regulator of Neisseria meningitidis, Acting both as a Repressor and as an Activator of Gene Transcription

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

Biochemistry and Molecular Biology Unit, Chiron Vaccines, 53100 Siena,1 Department of Biology, University of Bologna, 40126 Bologna, Italy2

Received 19 November 2004/ Accepted 2 February 2005

The crgA gene of Neisseria meningitidis, which codes for a LysR-type regulator, is divergently oriented with respect to the mdaB gene, which codes for a hypothetical NADPH-quinone oxidoreductase. Transcriptional studies of the intergenic region between crgA and mdaB showed that two overlapping and divergent promoters, PcrgA and PmdaB, control transcription of these genes. Deletion of the crgA gene led to a strong increase in transcription from the PcrgA promoter and a concomitant strong decrease in transcription from the PmdaB promoter, indicating that CrgA acts both as an autorepressor of transcription at its own promoter and as an activator of transcription at the mdaB promoter. Addition of {alpha}-methylene-{gamma}-butyrolactone (MBL), an inducer of NADPH-quinone oxidoreductase, to wild-type N. meningitidis cells specifically resulted in further activation of transcription of the PmdaB promoter and more repression of transcription of the PcrgA promoter. No such regulation was observed when MBL was added to crgA-deficient cells, indicating that the transcriptional response to MBL is CrgA mediated. Under the same experimental conditions, no regulation of transcription by either CrgA or MBL was detected at the pilus and capsule genes. The role of CrgA in the regulation of gene expression during the infectious cycle of N. meningitidis is discussed.

* Corresponding author. Mailing address: Biochemistry & Molecular Biology Unit, Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy. Phone: 39 0577 243565. Fax: 39 0577 243564. E-mail: enzo_scarlato{at}chiron.com.

{dagger} Present address: Institute of Microbiology, ETH-Hönggerberg HCI 4, Wolfgang-Pauli-Strasse, CH-8093 Zurich, Switzerland.

{ddagger} Present address: Cytos Biotechnology, Wagistrasse 25, CH-8952 Zurich-Schlieren, Switzerland.

Journal of Bacteriology, May 2005, p. 3421-3430, Vol. 187, No. 10
0021-9193/05/$08.00+0     doi:10.1128/JB.187.10.3421-3430.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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