Stapylococcus aureus ArcR Controls Expression of the Arginine Deiminase Operon

Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University Tel Aviv, 69978, Israel, and Institut für Mikrobiologie, Ernst-Moritz-Arndt Universität, F.-L.-Jahn-Str. 15, D-17487 Greifswald, Germany

^* To whom correspondence should be addressed. Email: yaira{at}post.tau.ac.il.

	Abstract

We identified in all sequenced Staphylococcus aureus genomes a single ORF that is strongly similar to ArcR a member of the Crp/Fnr family of bacterial transcriptional regulators. The arcR gene encoding ArcR forms an operon with the arginine deiminase (ADI) pathway genes arcABDC that enable utilization of arginine as a source of energy for growth under anaerobic conditions. In this report we show that under anaerobic conditions S. aureus growth is subject to glucose catabolic repression and is enhanced by arginine. Likewise, glucose and arginine have reciprocal effects on transcription of the arcABDCR genes. Further, we show using a mutant deleted for arcR, that transcription of the arc operon under anaerobic conditions strictly depends on a functional ArcR. These findings are supported by proteome analysis which shows that in anaerobic conditions expression of the ADI catabolic proteins depends on ArcR. Bioinformatic analysis of the S. aureus ArcR predicts a N-terminal nucleotide binding domain and a C-terminal helix-turn-helix DNA binding motif. We show that ArcR binds to a conserved Crp-like sequence motif TGTGA-N₆-TCACA present in the arc promoter region and thereby activates expression of the ADI pathway genes. Crp-like sequence motifs were also found in the regulatory regions of some 30 other S. aureus genes mostly encoding anaerobic enzymatic systems, virulence factors and regulatory systems. ArcR was tested and found to bind to the regulatory regions of four such genes adh1, lctE, srrAB and lukM. In one case, lctE encoding L-lactate dehydrogenase, ArcR was able to bind only in the presence of cAMP. These observations suggest that ArcR is likely to play an important role in the expression of numerous genes required for anaerobic growth.