Essential Bacterial Functions Encoded by Gene Pairs

Thomaides, Helena B.; Davison, Ella J.; Burston, Lisa; Johnson, H. E.; Brown, David R.; Hunt, Alison; Errington, Jeff; Czaplewski, Lloyd G.

doi:10.1128/jb.01381-06

Cited by 61 publications

(76 citation statements)

References 129 publications

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“…Noticeably, since fabHA codes for a ␤-ketoacyl-ACP synthase III as well, this gene is likely to take over the function of fabHB in the mutant strain tested. Recently, Thomaides et al (68) illustrated that the fabHA fabHB double mutant is nonviable. The combined treatment of cultures with both KS and cerulenin, the inhibitor of the ␤-ketoacyl-ACP synthases, significantly lowered the inhibitory effect of cerulenin alone (Fig.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling

et al. 2008

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The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong derepression of the CcpA, CodY, and Fur regulon and the induction of tricarboxylic acid cycle genes, SigL-and SigH-mediated genes, and the stringent response. Intriguingly, these conditions did not lead to the activation of sporulation, competence, or the general stress response. The fatty acid biosynthesis (fab) genes and BkdR-regulated genes are upregulated, which may indicate plasma membrane remodeling. This was further supported by the reduced sensitivity toward the fab inhibitor cerulenin upon sorbic acid stress. We are the first to present a comprehensive analysis of the transcriptional response of B. subtilis to sorbic acid stress.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling

et al. 2008

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“…B. subtilis encodes three enzymes (YbgE, YwaA, and Bcd) that can interconvert the branched-chain keto acids (BCKAs) and BCAAs (17,(45)(46)(47)(48) (Fig. 4A).…”

Section: Rna-seq Reveals a Graded Transcriptional Response Mediated Bymentioning

confidence: 99%

Hierarchical expression of genes controlled by theBacillus subtilisglobal regulatory protein CodY

Brinsmade

Alexander

Livny

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

105

119

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Global regulators that bind strategic metabolites allow bacteria to adapt rapidly to dynamic environments by coordinating the expression of many genes. We report an approach for determining gene regulation hierarchy using the regulon of the Bacillus subtilis global regulatory protein CodY as proof of principle. In theory, this approach can be used to measure the dynamics of any bacterial transcriptional regulatory network that is affected by interaction with a ligand. In B. subtilis, CodY controls dozens of genes, but the threshold activities of CodY required to regulate each gene are unknown. We hypothesized that targets of CodY are differentially regulated based on varying affinity for the protein's many binding sites. We used RNA sequencing to determine the transcription profiles of B. subtilis strains expressing mutant CodY proteins with different levels of residual activity. In parallel, we quantified intracellular metabolites connected to central metabolism. Strains producing CodY variants F71Y, R61K, and R61H retained varying degrees of partial activity relative to the WT protein, leading to gene-specific, differential alterations in transcript abundance for the 223 identified members of the CodY regulon. Using liquid chromatography coupled to MS, we detected significant increases in branched-chain amino acids and intermediates of arginine, proline, and glutamate metabolism, as well as decreases in pyruvate and glycerate as CodY activity decreased. We conclude that a spectrum of CodY activities leads to programmed regulation of gene expression and an apparent rerouting of carbon and nitrogen metabolism, suggesting that during changes in nutrient availability, CodY prioritizes the expression of specific pathways.BCAA | ILV | RNA-seq | metabolite analysis

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“…Indeed, after four IDAP cycles using 1.6 nM CodY, the fraction of reads corresponding to the ybgE region exceeded 70%, apparently indicating that this is the strongest CodY-binding region in the B. subtilis genome (Dataset S1D). The ybgE gene encodes a branched-chain amino acid aminotransferase (24,25).…”

Section: Genome-scale Identification Of B Subtilis Cody-binding Regimentioning

confidence: 99%

Genome-wide identification of Bacillus subtilis CodY-binding sites at single-nucleotide resolution

Belitsky

Sonenshein

2013

Proc. Natl. Acad. Sci. U.S.A.

102

154

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The CodY protein is a global transcriptional regulator that controls, directly or indirectly, expression of more than 100 genes and operons in Bacillus subtilis. We used in vitro DNA affinity purification combined with massively parallel sequencing, to identify B. subtilis chromosomal DNA fragments that bind CodY in vitro. A nonstandard strand-specific analysis of the data allowed us to pinpoint CodY-binding sites at single-nucleotide resolution. By comparing the extent of binding at decreasing CodY concentrations, we were able to classify binding regions according to their relative strengths and construct a subset of the 323 strongest CodY-binding regions that included sites associated with nearly all genes reported to be direct CodY targets. Many of the identified sites were located within coding regions. At such sites within the ispA, rapA, and rapE genes CodY-dependent repression was demonstrated using lacZ fusions and mutational analysis.

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Essential Bacterial Functions Encoded by Gene Pairs

Cited by 61 publications

References 129 publications

Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling

Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling

Hierarchical expression of genes controlled by theBacillus subtilisglobal regulatory protein CodY

Genome-wide identification of Bacillus subtilis CodY-binding sites at single-nucleotide resolution

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