The Fnr Regulon of Bacillus subtilis

Abstract

The Bacillus subtilis transcriptional regulator Fnr is an integral part of the regulatory cascade required for the adaptation of the bacterium to low oxygen tension. The B. subtilis Fnr regulon was defined via transcriptomic analysis in combination with bioinformatic-based binding site prediction. Four distinct groups of Fnr-dependent genes were observed. Group 1 genes (narKfnr, narGHJI, and arfM) are generally induced by Fnr under anaerobic conditions. All corresponding promoters contain an essential Fnr-binding site centered ؊41.5/؊40. The gram-positive model organism Bacillus subtilis adapts to an anaerobic environment by changing its metabolic activity (26). Under anaerobic conditions, B. subtilis performs a mixed-acid fermentation with lactate, acetate, and acetoin as the major products (7, 24). In the presence of nitrate, B. subtilis performs the respiratory process of ammonification (8,13,14,22).The regulatory network underlying anaerobic adaptation has been extensively studied during the last decade. A regulatory cascade describing the coordinated regulation of genes involved in anaerobiosis was established (7). One major regulatory switch in the adaptation to anaerobiosis is the two-component system ResDE (32,35). While the mechanism of signal perception by ResDE is still unknown, the downstream regulatory network is elucidated to a significant depth. Activated ResD binds to promoter regions of nasDE, encoding the nitrite reductase, the flavohemoglobin gene hmp, and the gene encoding the redox regulator Fnr (23, 25). Fnr in turn is responsible for the induction of the narGHJI operon and narK, encoding the respiratory nitrate reductase and a potential nitrite extrusion protein, respectively (6, 24). Mutation of fnr strongly affects anaerobic growth of B. subtilis on nitrate (6, 24). Furthermore, Fnr activates the expression of the arfM gene encoding an anaerobic respiration and fermentation modulator protein by direct interaction with the arfM promoter region (16). The promoter regions of all three Fnr-regulated genes carry the highly conserved potential B. subtilis Fnr-binding site (TGTGA-N 6 -TCACA) centered 41.5/40.5 bp from the transcriptional start point. Complementation experiments using an Escherichia coli crp mutant revealed that the DNA-binding domain of Fnr of B. subtilis is similar to that of Crp from E. coli, the well-studied cyclic AMP receptor protein (6). In B. subtilis, additional potential Fnr-binding sites were found in the promoter regions of a second potential nitrite transporter gene, ywcJ, as well as the fermentation operons ldh-lctP and alsSD (6,7,34). The latter operons encode lactate dehydrogenase, lactate permease, and acetolactate synthase and acetolactate decarboxylase, respectively. Transcription of alsSD and ldh-lctP was found to be anaerobically induced and repressed by the presence of nitrate (7). Nitrate repression was related to nitrate reductase activity (7).Global transcriptional profiling was used to analyze changes in the mRNA population after adaptation to anaerobic...

Regulon of the N -Acetylglucosamine Utilization Regulator NagR in Bacillus subtilis

“…Some NagR-dependent genes of the Fnr regulon, namely, the dhb and yku operons as well as cydC, were previously reported to also belong to the ferric uptake repressor (Fur) regulon (47), which controls the transcriptional response to iron starvation (3). Although expression of the fur gene itself is not strongly affected (1.4-fold upregulated in the nagR mutant), a total of 16 Fur-repressed genes were downregulated in strain FT20 (Table 3).…”

Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection inBacillus subtilisandStaphylococcus aureus

“…In a recent publication, the induction of a few genes encoding proteins involved in energy and fermentative metabolism has been demonstrated at the transcriptional level, including the L-lactate dehydrogenase ldh1 and 1,6-fructosebisphosphate aldolase fdaB (83). As the protein expression analysis makes more clear, the induction of anaerobic gene expression by NO, even in the presence of oxygen, would be a major difference compared to B. subtilis, where low oxygen tension is a prerequisite for the induction of genes involved in anaerobic respiration and fermentation (64,82). The main reason for this might be the strict oxygen sensitivity of Fnr, which is a main regulator in the adaptation to anaerobic conditions in B. subtilis (81,82).…”

Regulation of the nitrate reductase operon narKGHJI by the cAMP-dependent regulator GlxR in Corynebacterium glutamicum

“…Consequently, it is suggested that GlxR is not directly associated with the sensing mechanism for the anaerobiosis-responsive induction of narKGHJI expression. The regulation of narKGHJI expression by ArnR and CRP-type GlxR regulators in C. glutamicum is quite different from the well-known FNR-dependent anaerobic induction of the nitrate reductase gene expression in E. coli and B. subtilis (Bonnefoy & Demoss, 1994;Reents et al, 2006). In Shewanella oneidensis MR-1, a metal reducer that uses more than 14 terminal electron acceptors for respiration, instead of EtrA (an FNR homologue), CRP is involved in positive regulation of a variety of anaerobic respiration including nitrate, DMSO, fumarate and Fe(III) reduction (Saffarini et al, 2003).…”