During growth of Bacillus subtilis in nutrient sporulation medium containing histidine (DSM-His medium), the expression of histidase, the first enzyme in the histidine-degradative pathway (hut), is derepressed 40-to 200- When Bacillus subtilis cultures enter stationary growth phase in nutrient sporulation medium, the expression of gene products which allow the bacteria to adapt to their altered growth conditions is derepressed. Cells become motile, secrete a number of degradative enzymes, synthesize antibiotics, and, ultimately, can initiate the process of sporulation (28,30,32). All of these processes help the cells to survive under environmental conditions which are not optimal for growth.We have been studying the regulation of the enzymes responsible for histidine utilization (hut) in B. subtilis. The genes encoding the four enzymes that catalyze histidine degradation are organized as a multicistronic operon in B. subtilis (5,17,26). The first open reading frame in the hut operon, hutP, encodes a regulatory protein, which activates hut expression in trans (10,26). Downstream of the hutP gene is the hutH gene, which encodes histidase, the first enzyme in histidine degradation (26). A nucleotide sequence which could form a stem-loop structure lies between the hutP and hutH genes. Antitermination of hut transcription at this putative stem-loop structure has been proposed to mediate histidine-dependent induction of hut expression (26).Expression of the hut operon is highly regulated in response to nutrient availability in B. subtilis. hut expression is induced by histidine and repressed by rapidly metabolizable carbon compounds such as glucose, glycerol, or malate (5). Growth in the presence of a mixture of amino acids strongly inhibits synthesis of the hut enzymes (2). Mutations which alter regulation of the hut operon have been isolated. The * Corresponding author. hutC1 mutation allows expression of the hut enzymes in the absence of the inducer, histidine (5). hut expression is insensitive to regulation by catabolite repression in strains containing the hutR4 mutation (2, 11). Both the hutCl and hutR4 mutations are tightly linked to the hutH locus by transformation (5, 11).In this article, we report that hut expression is repressed during exponential growth in nutrient sporulation medium, but its expression completely derepresses at the onset of stationary growth phase. The postexponential activation of hut expression in this medium was investigated to identify factors regulating gene expression during this period of environmental stress. Derepression of hut expression during stationary growth in nutrient sporulation medium appears to be mediated primarily by the relief of amino acid repression of histidine transport.
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