Genomewide transcriptional changes associated with genetic alterations and nutritional supplementation affecting tryptophan metabolism in Bacillus subtilis

DNA microarrays comprising approximate to95% of the Bacillus subtilis annotated protein coding ORFs were deployed to generate a series of snapshots of genomewide transcriptional changes that occur when cells are grown under various conditions that are expected to increase or decrease transcription of the trp operon segment of the aromatic supraoperon. Comparisons of global expression patterns were made between cells grown in the presence of indole acrylic acid, a specific inhibitor of tRNA(Trp) charging; cells deficient in expression of the mtrB gene, which encodes the tryptophanactivated negative regulatory protein, TRAP; WT cells grown in the presence or absence of two or three of the aromatic amino acids; and cells harboring a tryptophanyl tRNA synthetase mutation conferring temperature-sensitive tryptophan-dependent growth. Our findings validate expected responses of the tryptophan biosynthetic genes and presumed regulatory interrelationships between genes in the different aromatic amino acid pathways and the histidine biosynthetic pathway. Using a combination of supervised and unsupervised statistical methods we identified approximate to100 genes whose expression profiles were closely correlated with those of the genes in the trp operon. This finding suggests that expression of these genes is influenced directly or indirectly by regulatory events that affect or are a consequence of altered tryptophan metabolism.