Genetic Control of Osmoadaptive Glycine Betaine Synthesis in Bacillus subtilis through the Choline-Sensing and Glycine Betaine-Responsive GbsR Repressor

Nau-Wagner, Gabriele; Opper, Daniela; Rolbetzki, Anne; Boch, Jens; Kempf, Bettina; Hoffmann, Tamara; Bremer, Erhard

doi:10.1128/jb.06642-11

Cited by 52 publications

(173 citation statements)

References 62 publications

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“…P. aeruginosa maintains a cytoplasmic choline pool under a variety of conditions and even under conditions in which extracellular choline is depleted by active transport (65). It is not known if this choline pool is maintained by regulation of BetA and BetB enzyme activity directly, via balance of BetI repression, or if GB acts to repress expression or activity of this catabolic step as GbsR does in B. subtilis (55). In P. aeruginosa, the choline and GB pools are linked, but their regulation is not completely coupled.…”

Section: Regulation Of Aerobic Choline and Gb Catabolism In Pseudomonadsmentioning

confidence: 99%

Homeostasis and Catabolism of Choline and Glycine Betaine: Lessons from Pseudomonas aeruginosa

Wargo

2013

Appl Environ Microbiol

155

121

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Most sequenced bacteria possess mechanisms to import choline and glycine betaine (GB) into the cytoplasm. The primary role of choline in bacteria appears to be as the precursor to GB, and GB is thought to primarily act as a potent osmoprotectant. Choline and GB may play accessory roles in shaping microbial communities, based on their limited availability and ability to enhance survival under stress conditions. Choline and GB enrichment near eukaryotes suggests a role in the chemical relationships between these two kingdoms, and some of these interactions have been experimentally demonstrated. While many bacteria can convert choline to GB for osmoprotection, a variety of soil-and water-dwelling bacteria have catabolic pathways for the multistep conversion of choline, via GB, to glycine and can thereby use choline and GB as sole sources of carbon and nitrogen. In these choline catabolizers, the GB intermediate represents a metabolic decision point to determine whether GB is catabolized or stored as an osmo-and stress protectant. This minireview focuses on this decision point in Pseudomonas aeruginosa, which aerobically catabolizes choline and can use GB as an osmoprotectant and a nutrient source. P. aeruginosa is an experimentally tractable and ecologically relevant model to study the regulatory pathways controlling choline and GB homeostasis in choline-catabolizing bacteria. The study of P. aeruginosa associations with eukaryotes and other bacteria also makes this a powerful model to study the impact of choline and GB, and their associated regulatory and catabolic pathways, on host-microbe and microbe-microbe relationships.

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Section: Regulation Of Aerobic Choline and Gb Catabolism In Pseudomonadsmentioning

confidence: 99%

Homeostasis and Catabolism of Choline and Glycine Betaine: Lessons from Pseudomonas aeruginosa

Wargo

2013

Appl Environ Microbiol

155

121

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“…We have demonstrated that it is not choline itself, but rather GB, that is important for P. aeruginosa survival in the mammalian lung (11). GB alters gene transcription via unknown mechanisms from promoters controlled by BetI and GbsR (12)(13)(14), but the only specific GB-sensing transcription factor currently described in bacteria is GbdR. Therefore, we were interested in the scope of GbdR transcriptional control in P. aeruginosa.…”

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confidence: 99%

Characterization of the GbdR Regulon in Pseudomonas aeruginosa

Hampel

LaBauve

Meadows

et al. 2013

Journal of Bacteriology

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Pseudomonas aeruginosa displays tremendous metabolic diversity, controlled in part by the abundance of transcription regulators in the genome. We have been investigating P. aeruginosa's response to the host, particularly changes regulated by the hostderived quaternary amines choline and glycine betaine (GB). We previously identified GbdR as an AraC family transcription factor that directly regulates choline acquisition from host phospholipids (via binding to plcH and pchP promoters), is required for catabolism of the choline metabolite GB, and is an activator that induces transcription in response to GB or dimethylglycine. Our goal was to characterize the GbdR regulon in P. aeruginosa by using genetics and chemical biology in combination with transcriptomics and in vitro DNA-binding assays. Here we show that GbdR activation regulates transcription of 26 genes from 12 promoters, 11 of which have measureable binding to GbdR in vitro. The GbdR regulon includes the genes encoding GB, dimethylglycine, sarcosine, glycine, and serine catabolic enzymes and the BetX and CbcXWV quaternary amine transport proteins. We characterized the GbdR consensus binding site and used it to identify that the recently characterized acetylcholine esterase gene, choE (PA4921), is also regulated by GbdR. The regulon member not directly controlled by GbdR is the secreted lipase gene lipA, which was also the only regulon member repressed under GbdR-activating conditions. Determination of the GbdR regulon provides deeper understanding of how GbdR links bacterial metabolism and virulence. Additionally, identification of two uncharacterized regulon members suggests roles for these proteins in response to choline metabolites.

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“…(12,20). The synthesis of glycine betaine from the precursor choline (taken up via the OpuB and OpuC transporters) is catalyzed through a two-step oxidation process by the GbsB and GbsA enzymes, with glycine betaine aldehyde as the intermediate (24,25). The anabolic and osmoadaptive proline biosynthetic routes and their genetic control have been described elsewhere (9,19).…”

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confidence: 99%

“…Synthesis of glycine betaine relies on the uptake of the precursor molecule choline (via OpuB and OpuC) (23), which then undergoes a two-step oxidation reaction catalyzed by the GbsB and GbsA enzymes to produce glycine betaine ( Fig. 1) (24,25). The ABC transporters OpuA and OpuC and the BCCT (betaine-choline-carnitine-transporter)-type carrier OpuD mediate the import of glycine betaine ( Fig.…”

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confidence: 99%

Osmotic Control of opuA Expression in Bacillus subtilis and Its Modulation in Response to Intracellular Glycine Betaine and Proline Pools

Hoffmann¹,

Wensing²,

Brosius³

et al. 2012

Journal of Bacteriology

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172

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bGlycine betaine is an effective osmoprotectant for Bacillus subtilis. Its import into osmotically stressed cells led to the buildup of large pools, whose size was sensitively determined by the degree of the osmotic stress imposed. The amassing of glycine betaine caused repression of the formation of an osmostress-adaptive pool of proline, the only osmoprotectant that B. subtilis can synthesize de novo. The ABC transporter OpuA is the main glycine betaine uptake system of B. subtilis. Expression of opuA was upregulated in response to both sudden and sustained increases in the external osmolarity. Nonionic osmolytes exerted a stronger inducing effect on transcription than ionic osmolytes, and this was reflected in the development of corresponding OpuA-mediated glycine betaine pools. Primer extension analysis and site-directed mutagenesis pinpointed the osmotically controlled opuA promoter. Deviations from the consensus sequence of SigA-type promoters serve to keep the transcriptional activity of the opuA promoter low in the absence of osmotic stress. opuA expression was downregulated in a finely tuned manner in response to increases in the intracellular glycine betaine pool, regardless of whether this osmoprotectant was imported or was newly synthesized from choline. Such an effect was also exerted by carnitine, an effective osmoprotectant for B. subtilis that is not a substrate for the OpuA transporter. opuA expression was upregulated in a B. subtilis mutant that was unable to synthesize proline in response to osmotic stress. Collectively, our data suggest that the intracellular solute pool is a key determinant for the osmotic control of opuA expression.

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Genetic Control of Osmoadaptive Glycine Betaine Synthesis in Bacillus subtilis through the Choline-Sensing and Glycine Betaine-Responsive GbsR Repressor

Cited by 52 publications

References 62 publications

Homeostasis and Catabolism of Choline and Glycine Betaine: Lessons from Pseudomonas aeruginosa

Homeostasis and Catabolism of Choline and Glycine Betaine: Lessons from Pseudomonas aeruginosa

Characterization of the GbdR Regulon in Pseudomonas aeruginosa

Osmotic Control of opuA Expression in Bacillus subtilis and Its Modulation in Response to Intracellular Glycine Betaine and Proline Pools

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