Global transcriptional control by NsrR in Bacillus subtilis

The NO-sensitive NsrR repressor of Bacillus subtilis, which carries a [4Fe-4S] cluster, controls transcription of nasD and hmp(class I regulation) under anaerobic conditions. Here, we describe another class of NsrR regulation (class II regulation) that controlsa more diverse collection of genes. Base substitution analysis showed that [4Fe-4S]-NsrR recognizes a partial dyad symmetrywithin the class I cis-acting sites, whereas NO-insensitive interaction of NsrR with an A+T-rich class II regulatory siteshowed relaxed sequence specificity. Genome-wide transcriptome studies identified genes that are under the control of the classII NsrR regulation. The class II NsrR regulon includes genes controlled by both AbrB and Rok repressors, which also recognizeA+T-rich sequences, and by the Fur repressor. Transcription of class II genes was elevated in an nsrR mutant during anaerobicfermentative growth with pyruvate. Although NsrR binding to the class II regulatory sites was NO insensitive in vitro, transcriptionof class II genes was moderately induced by NO, which involved reversal of NsrR-dependent repression, suggesting thatclass II repression is also NO sensitive. In all NsrR-repressed genes tested, the loss of NsrR repressor activity was not sufficient toinduce transcription as induction required the ResD response regulator. The ResD-ResE signal transduction system is essentialfor activation of genes involved in aerobic and anaerobic respiration. This study indicated coordinated regulation between ResDand NsrR and uncovered a new role of ResD and NsrR in transcriptional regulation during anaerobiosis of B. subtilis.