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Global Control of Cysteine Metabolism by CymR in Bacillus subtilis

Sergine Even, Pierre Burguière, Sandrine Auger, Olga Soutourina, Antoine Danchin, and Isabelle Martin-Verstraete^*

Unité de Génétique des Génomes Bactériens, Institut Pasteur, URA CNRS 2171, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France

Received 17 October 2005/ Accepted 22 December 2005

YrzC has previously been identified as a repressor controlling ytmI expression via its regulation of YtlI activator synthesis in Bacillus subtilis. We identified YrzC as a master regulator of sulfur metabolism. Gene expression profiles of B. subtilis yrzC mutant and wild-type strains grown in minimal medium with sulfate as the sole sulfur source were compared. In the mutant, increased expression was observed for 24 genes previously identified as repressed in the presence of sulfate. Since several genes involved in the pathways leading to cysteine formation were found, we propose to rename YrzC CymR, for "cysteine metabolism repressor." A CymR-dependent binding to the promoter region of the ytlI, ssuB, tcyP, yrrT, yxeK, cysK, or ydbM gene was demonstrated using gel shift experiments. A potential CymR target site, TAAWNCN₂ANTWNAN₃ATMGGAATTW, was found in the promoter region of these genes. In a DNase footprint experiment, the protected region in the ytlI promoter region contained this consensus sequence. Partial deletion or introduction of point mutations in this sequence confirmed its involvement in ytlI, yrrT, and yxeK regulation. The addition of O-acetylserine in gel shift experiments prevented CymR-dependent binding to DNA for all of the targets characterized. Transcriptome analysis of a cymR mutant and the wild-type strain also brought out significant changes in the expression level of a large set of genes related to stress response or to transition toward anaerobiosis.

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

Present address: Laboratoire de Microbiologie UMR1055 Ecole Supérieure Agronomique de Rennes, INRA, 65 rue de Saint Brieuc, 35042 Rennes Cedex, France.

Present address: Unité de Génétique Microbienne, INRA, Domaine de Vilvert, 78352 Jouy en Josas, France.

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