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Journal of Bacteriology, December 2009, p. 7260-7269, Vol. 191, No. 23
0021-9193/09/$08.00+0     doi:10.1128/JB.01009-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of the Transcriptional Regulator RamB (Rv0465c) in the Control of the Glyoxylate Cycle in Mycobacterium tuberculosis{triangledown} ,{dagger}

Julia C. Micklinghoff,1 Katrin J. Breitinger,2 Mascha Schmidt,1 Robert Geffers,3 Bernhard J. Eikmanns,2* and Franz-Christoph Bange1*

Department of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany,1 Institute of Microbiology and Biotechnology, University of Ulm, 89069 Ulm, Germany,2 Department of Cell Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany3

Received 30 July 2009/ Accepted 11 September 2009

Mycobacterium tuberculosis generally is assumed to depend on lipids as a major carbon and energy source when persisting within the host. The utilization of fatty acids requires a functional glyoxylate cycle with the key enzymes isocitrate lyase (Icl) and malate synthase. The open reading frame Rv0465c of M. tuberculosis H37Rv encodes a protein with significant sequence similarity to the transcriptional regulator RamB, which in Corynebacterium glutamicum controls the expression of several genes involved in acetate metabolism, i.e., those encoding enzymes of acetate activation and the glyoxylate cycle. We show here that the M. tuberculosis Rv0465c protein can functionally complement RamB in C. glutamicum and that it binds to the promoter regions of M. tuberculosis icl1 and Rv0465c. Construction and subsequent transcriptional and enzymatic analysis of a defined Rv0465c deletion mutant in M. tuberculosis revealed that the Rv0465c protein, now designated RamB, represses icl1 expression during growth with glucose and negatively autoregulates the expression of its own operon. Whole-genome microarray analysis of the M. tuberculosis ramB (ramBMT) mutant and the wild type furthermore showed that apart from icl1 and the ramBMT operon, the expression of all other M. tuberculosis genes involved in acetate metabolism remain unchanged in the mutant. Thus, RamBMT has a more specific regulatory function as RamB from C. glutamicum and is confined to expression control of icl1 and the ramBMT operon.

* Corresponding author. Mailing address for F.-C. Bange: Department of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Phone: 49 511 532 4359. Fax: 49 511 532 4366. E-mail: bange.franz{at}mh-hannover.de. Mailing address for B. Eikmanns: Institute of Microbiology and Biotechnology, University of Ulm, 89069 Ulm, Germany. Phone: 49 731 50 22707. Fax: 49 731 50 22719. E-mail: bernhard.eikmanns{at}uni-ulm.de

{triangledown} Published ahead of print on 18 September 2009.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, December 2009, p. 7260-7269, Vol. 191, No. 23
0021-9193/09/$08.00+0     doi:10.1128/JB.01009-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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