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J. Bacteriol. doi:10.1128/JB.01395-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Role of RelA of Streptococcus mutans in Global Control of Gene Expression

Department of Oral Biology, University of Florida College of Dentistry, Gainesville, Florida 32610

^* To whom correspondence should be addressed. Email: rburne{at}dental.ufl.edu.

	Abstract

The production of (p)ppGpp by Streptococcus mutans UA159 is catalyzed by three gene products, RelA, RelP and RelQ. Here, we investigate the role of the RelA (Rel) homologue of S. mutans in the stringent response and in global control of gene expression. RelA of S. mutans was shown to synthesize pppGpp in vitro from GTP and ATP in the absence of added ribosomes, as well as in vivo in an E. coli relA-spoT mutant. Mupirocin (MUP) was shown to induce high levels of (p)ppGpp production in S. mutans in a relA-dependent manner, with a concomitant reduction in GTP pools. Transcription profiling following MUP treatment of S. mutans revealed that 104 genes were up-regulated and 130 down-regulated (P 0.001); mainly genes for macromolecular biosynthesis, translation and energy metabolism were down-regulated. When a derivative of UA159 carrying a complete deletion of the relA gene was treated with MUP, 72 genes were up-regulated and 52 down-regulated (P 0.001). The expression of 50 genes (P 0.001) was commonly affected by MUP-treatment in the two strains, suggesting that S. mutans can mount a relA-independent response to MUP. Consistent with the gene expression profiling, RelA was shown to play major roles in the regulation of phenotypic traits that are required for establishment, persistence and virulence expression by this oral pathogen. Thus, RelA is the major (p)ppGpp synthase controlling the stringent response in S. mutans, and it coordinates the expression of genes and phenotypes that contribute to the pathogenic potential of the organism.

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