Proline to the rescue

Fisher, Mark T.

doi:10.1073/pnas.0606106103

Cited by 33 publications

(16 citation statements)

References 20 publications

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“…This applies both to an osmotic downshift that requires the rapid expulsion of water-attracting solutes from the cell through the transient opening of mechanosensitive channels to avert cell lysis (29,63) and to an increase in the osmolarity that requires the accumulation of water-attracting solutes to prevent dehydration of the cytoplasm and growth arrest (8,9,64). We address here the latter aspect of the B. subtilis osmostress response by focusing on the osmoadaptive synthesis of proline, a compatible solute that is widely used by microorganisms as an osmostress protectant (15,21,41,66). It has been known through the pioneering study by Measures (46) and subsequent detailed physiological investigations by Whatmore et al (64) that B. subtilis synthesizes very large quantities of proline in response to high salinity.…”

Section: Discussionmentioning

confidence: 99%

“…Proline is a compatible solute that is widely used in nature by both pro-and eukaryotic cells to fend off the detrimental effects of high osmolarity on cell physiology (15,41,66). It also exhibits protein-stabilizing properties and promotes protein folding under unfavorable conditions (21,35,60).In many microorganisms, proline biosynthesis proceeds from the precursor glutamate and involves three enzyme-catalyzed steps (Fig. 1D) (16).…”

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Osmotically Controlled Synthesis of the Compatible Solute Proline Is Critical for Cellular Defense of Bacillus subtilis against High Osmolarity

et al. 2011

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Bacillus subtilis is known to accumulate large amounts of the compatible solute proline via de novo synthesis as a stress protectant when it faces high-salinity environments. We elucidated the genetic determinants required for the osmoadaptive proline production from the precursor glutamate. This proline biosynthesis route relies on the proJ-encoded ␥-glutamyl kinase, the proA-encoded ␥-glutamyl phosphate reductase, and the proH-encoded ⌬ 1 -pyrroline-5-caboxylate reductase. Disruption of the proHJ operon abolished osmoadaptive proline production and strongly impaired the ability of B. subtilis to cope with high-osmolarity growth conditions. Disruption of the proA gene also abolished osmoadaptive proline biosynthesis but caused, in contrast to the disruption of proHJ, proline auxotrophy. Northern blot analysis demonstrated that the transcription of the proHJ operon is osmotically inducible, whereas that of the proBA operon is not. Reporter gene fusion studies showed that proHJ expression is rapidly induced upon an osmotic upshift. Increased expression is maintained as long as the osmotic stimulus persists and is sensitively linked to the prevalent osmolarity of the growth medium. Primer extension analysis revealed the osmotically controlled proHJ promoter, a promoter that resembles typical SigA-type promoters of B. subtilis. Deletion analysis of the proHJ promoter region identified a 126-bp DNA segment carrying all sequences required in cis for osmoregulated transcription. Our data disclose the presence of ProA-interlinked anabolic and osmoadaptive proline biosynthetic routes in B. subtilis and demonstrate that the synthesis of the compatible solute proline is a central facet of the cellular defense to high-osmolarity surroundings for this soil bacterium.The soil-dwelling bacterium Bacillus subtilis (20) is frequently exposed to osmotic fluctuations in its environment as a consequence of wetting and drying cycles of the upper layers of the soil (8). As a result of these changes in the osmolarity and salinity of the habitat, the B. subtilis cell has to cope with osmotically instigated water fluxes across the cytoplasmic membrane. Consequently, the integrity of the cell is threatened under hypo-osmotic conditions, or its growth is impaired under hyperosmotic conditions (8). No microorganism can actively pump water in or out of the cell to compensate for water fluxes caused by changes in the external osmotic condition. Instead, microorganisms determine the direction and scale of water permeation across the cytoplasmic membrane indirectly by actively controlling the osmotic potential of their cytoplasm (9,66). This is often accomplished under high-osmolarity conditions by first importing large amounts of potassium as an emergency stress reaction (9,41,66). Subsequently, the cell replaces part of the accumulated potassium by a distinct class of highly water-soluble organic compounds, the compatible solutes (11). These osmolytes have been specifically selected in the course of evolution as effective osmo-and cytoprote...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Osmotically Controlled Synthesis of the Compatible Solute Proline Is Critical for Cellular Defense of Bacillus subtilis against High Osmolarity

et al. 2011

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“…L-Proline is a well-known representative of this class of compounds (Csonka, 1989;Kempf & Bremer, 1998). In addition to its role as a water-attracting organic osmolyte, the function-preserving properties of L-proline for macromolecules provide an additional level of cellular protection for bacterial cells challenged by high osmolarity (Fisher, 2006;Ignatova & Gierasch, 2006;Street et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Plant-derived compatible solutes proline betaine and betonicine confer enhanced osmotic and temperature stress tolerance to Bacillus subtilis

et al. 2014

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L-Proline is a widely used compatible solute and is employed by Bacillus subtilis, through both synthesis and uptake, as an osmostress protectant. Here, we assessed the stress-protective potential of the plant-derived L-proline derivatives N-methyl-L-proline, L-proline betaine (stachydrine), trans-4-L-hydroxproline and trans-4-hydroxy-L-proline betaine (betonicine) for cells challenged by high salinity or extremes in growth temperature. L-Proline betaine and betonicine conferred salt stress protection, but trans-4-L-hydroxyproline and N-methyl-L-proline was unable to do so. Except for L-proline, none of these compounds served as a nutrient for B. subtilis.L-Proline betaine was a considerably better osmostress protectant than betonicine, and its import strongly reduced the L-proline pool produced by B. subtilis under osmotic stress conditions, whereas a supply of betonicine affected the L-proline pool only modestly. Both compounds downregulated the transcription of the osmotically inducible opuA operon, albeit to different extents. Mutant studies revealed that L-proline betaine was taken up via the ATP-binding cassette transporters OpuA and OpuC, and the betaine-choline-carnitine-transporter-type carrier OpuD; betonicine was imported only through OpuA and OpuC. L-Proline betaine and betonicine also served as temperature stress protectants. A striking difference between these chemically closely related compounds was observed: L-proline betaine was an excellent cold stress protectant, but did not provide heat stress protection, whereas the reverse was true for betonicine. Both compounds were primarily imported in temperature-challenged cells via the high-capacity OpuA transporter. We developed an in silico model for the OpuAC-betonicine complex based on the crystal structure of the OpuAC solute receptor complexed with L-proline betaine.

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“…In addition to its function as a water-attracting osmolyte, proline also serves as a "chemical chaperone" (8) by aiding the proper folding of proteins and by preventing their aggregation in osmotically challenged cells (9). The soil-dwelling bacterium Bacillus subtilis makes use of proline as an osmoprotectant through both de novo synthesis and uptake (6,(10)(11)(12).…”

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Osmoprotection of Bacillus subtilis through Import and Proteolysis of Proline-Containing Peptides

Zaprasis

Brill

Thüring

et al. 2013

Appl Environ Microbiol

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Bacillus subtilis can attain cellular protection against the detrimental effects of high osmolarity through osmotically induced de novo synthesis and uptake of the compatible solute L-proline. We have now found that B. subtilis can also exploit exogenously provided proline-containing peptides of various lengths and compositions as osmoprotectants. Osmoprotection by these types of peptides is generally dependent on their import via the peptide transport systems (

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Proline to the rescue

Cited by 33 publications

References 20 publications

Osmotically Controlled Synthesis of the Compatible Solute Proline Is Critical for Cellular Defense of Bacillus subtilis against High Osmolarity

Osmotically Controlled Synthesis of the Compatible Solute Proline Is Critical for Cellular Defense of Bacillus subtilis against High Osmolarity

Plant-derived compatible solutes proline betaine and betonicine confer enhanced osmotic and temperature stress tolerance to Bacillus subtilis

Osmoprotection of Bacillus subtilis through Import and Proteolysis of Proline-Containing Peptides

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