Changes in lipid and proteome composition accompany growth ofBacillus subterraneusMITOT1 under supercritical CO2and may promote acclimation to associated stresses

AbstractRecent demonstration that multipleBacillusstrains grow in batch bioreactors containing supercritical (sc) CO2(i.e. >73 atm, >31°C) is surprising given the recognized roles of scCO2as a sterilant and solvent. Growth under scCO2is of interest for biotechnological applications and for microbially-enhanced geologic carbon sequestration. We hypothesize thatBacillusspp. may alter cell wall and membrane composition in response to scCO2-associated stresses. In this study, protein expression and membrane lipids ofB. subterraneusMITOT1 were profiled in cultures grown under headspaces of 1 and 100 atm of CO2or N2. Growth under 100 atm CO2revealed significantly decreased fatty acid branching and increased fatty acyl chain lengths relative to 1 atm cultures. Proteomes of MITOT1 grown under 1 and 100 atm pressures of CO2and N2were similar (Spearman R>0.65), and principal component analysis revealed variation by treatment with the first two principal components corresponding to headspace gas (CO2or N2) and pressure (1 atm and 100 atm), respectively. Amino acid metabolic proteins were enriched under CO2, including the glycine cleavage system, previously shown to be upregulated in acid stress response. These results provide insights into the stationary phase physiology of strains grown under scCO2, suggesting modifications of cell membranes and amino acid metabolism may be involved in response to acidic, high CO2conditions under scCO2.

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Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids

10.1101/2021.06.01.446428 ◽

2021 ◽

Author(s):

S'Dravious Arkius DeVeaux ◽

Molly E Ogle ◽

Sofiya Vyshnya ◽

Nathan F Chiappa ◽

Bobby Leitmann ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Acyl Chain ◽

Principal Component ◽

Fatty Acyl ◽

Fatty Acyl Chain ◽

Bioactive Lipids ◽

Cell Therapies ◽

Linear Discriminant

Cell therapies are expected to increase over the next decade due to increasing demand for clinical applications. Mesenchymal stromal cells (MSCs) have been explored to treat a number of diseases, with some successes in early clinical trials. Despite early successes, poor MSC characterization results in lessened therapeutic capacity once in vivo. Here, we characterized bone marrow (BM), adipose derived and umbilical cord tissue MSCs sphingolipids (SLs), a class of bioactive lipids, using liquid chromatography tandem mass spectrometry. We found ceramide levels differed based upon donors sex in BM MSCs. We detected fatty acyl chain variants in MSCs from all 3 sources. Principal component analysis showed IFNg; primed and untreated MSCs separated according to their SL signature. We detected higher ceramide levels in low IDO MSCs, indicating sphingomeylinase or ceramidase enzymatic activity may be involved in their immune potency. Lastly, linear discriminant analysis revealed that MSCs separated based on tissue source.

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Fatty acyl chain structure, orientational order, and the lipid phase transition in Acholeplasma laidlawii B membranes. A review of recent 19F nuclear magnetic resonance studies

Canadian Journal of Biochemistry and Cell Biology ◽

10.1139/o84-147 ◽

1984 ◽

Vol 62 (11) ◽

pp. 1134-1150 ◽

Cited By ~ 16

Author(s):

P. M. Macdonald ◽

B. D. Sykes ◽

R. N. McElhaney

Keyword(s):

Phase Transition ◽

Fatty Acids ◽

Nuclear Magnetic Resonance ◽

Acyl Chain ◽

Orientational Order ◽

Membrane Lipid ◽

Fatty Acyl ◽

Fatty Acyl Chain ◽

Lipid Phase ◽

Lipid Phase Transition

The orientational order parameters of monofluoropalmitic acids biosynthetically incorporated into membranes of Acholeplasma laidlawii B in the presence of a large excess of a variety of structurally diverse fatty acids have been determined via 19F nuclear magnetic resonance (19F NMR) spectroscopy. It is demonstrated that these monofluoropalmitic acids are relatively nonperturbing membrane probes based upon physical (differential scanning calorimetry), biochemical (membrane lipid analysis), and biological (growth studies) criteria. 19F NMR is shown to convey the same qualitative and quantitative picture of membrane lipid order provided by 2H-NMR techniques and to be sensitive to the structural characteristics of the membrane fatty acyl chains, as well as to the lipid phase transition. Representatives of each naturally occurring class of fatty acyl chain structures, including straight-chain saturated, methyl-branched, monounsaturated, and alicyclic-ring-substituted fatty acids, were studied and the 19F-NMR order parameters were correlated with the lipid phase transitions (determined calorimetrically). The lipid phase transition was the prime determinant of overall orientational order regardless of fatty acid structure. Effects upon orientational order attributable to specific structural substituents were discernible, but were secondary to the effects of the lipid phase transition. In the gel state, relative overall order was directly proportional to the temperature of the particular lipid phase transition. Not only the overall order, but also the order profile across the membrane was sensitive to the presence of particular structural substituents. In particular, in the gel state specific fatty acyl structures demonstrated a characteristic disordering effect in the membrane order profile. These various observations can be merged to provide a unified picture of the manner in which fatty acyl chain chemistry modulates the physical state of membrane lipids.

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The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy

Cancers ◽

10.3390/cancers13102475 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2475

Author(s):

Megan Sheridan ◽

Besim Ogretmen

Keyword(s):

Cancer Therapy ◽

Acyl Chain ◽

Fatty Acyl ◽

Fatty Acyl Chain ◽

Cancer Cell Proliferation ◽

Bioactive Lipids ◽

Cellular Functions ◽

Proliferation Response ◽

Ceramide Synthases

Sphingolipids are bioactive lipids responsible for regulating diverse cellular functions such as proliferation, migration, senescence, and death. These lipids are characterized by a long-chain sphingosine backbone amide-linked to a fatty acyl chain with variable length. The length of the fatty acyl chain is determined by specific ceramide synthases, and this fatty acyl length also determines the sphingolipid’s specialized functions within the cell. One function in particular, the regulation of the selective autophagy of mitochondria, or mitophagy, is closely regulated by ceramide, a key regulatory sphingolipid. Mitophagy alterations have important implications for cancer cell proliferation, response to chemotherapeutics, and mitophagy-mediated cell death. This review will focus on the alterations of ceramide synthases in cancer and sphingolipid regulation of lethal mitophagy, concerning cancer therapy.

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Effect of fatty acyl chain length and structure on the lamellar gel to liquid-crystalline and lamellar to reversed hexagonal phase transitions of aqueous phosphatidylethanolamine dispersions

Biochemistry ◽

10.1021/bi00428a020 ◽

1989 ◽

Vol 28 (2) ◽

pp. 541-548 ◽

Cited By ~ 87

Author(s):

Ruthven N. A. H. Lewis ◽

David A. Mannock ◽

Ronald N. McElhaney ◽

David C. Turner ◽

Sol M. Gruner

Keyword(s):

Phase Transitions ◽

Chain Length ◽

Liquid Crystalline ◽

Hexagonal Phase ◽

Acyl Chain ◽

Fatty Acyl ◽

Fatty Acyl Chain ◽

Acyl Chain Length

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Effect of Acylglycerol Composition and Fatty Acyl Chain Length on Lipid Digestion in pH-Stat Digestion Model and SimulatedIn VitroDigestion Model

Journal of Food Science ◽

10.1111/1750-3841.13196 ◽

2015 ◽

Vol 81 (2) ◽

pp. C317-C323

Author(s):

Jin F. Qi ◽

Cai H. Jia ◽

Jung A. Shin ◽

Jeong M. Woo ◽

Xiang Y. Wang ◽

...

Keyword(s):

Chain Length ◽

Acyl Chain ◽

Fatty Acyl ◽

Fatty Acyl Chain ◽

Lipid Digestion ◽

Acyl Chain Length ◽

Ph Stat

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Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014122 ◽

2020 ◽

Vol 295 (28) ◽

pp. 9268-9280 ◽

Cited By ~ 3

Author(s):

Adriana Osickova ◽

Humaira Khaliq ◽

Jiri Masin ◽

David Jurnecka ◽

Anna Sukova ◽

...

Keyword(s):

Acyl Chain ◽

Fatty Acyl ◽

Biologically Active ◽

Fatty Acyl Chain ◽

Acyl Carrier Proteins ◽

E Coli ◽

Rtx Toxins ◽

Wide Range ◽

Lysine Residues ◽

Acyl Chains

In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. Bacterial repeats in toxin (RTX) cytolysins form a prominent group of proteins that are synthesized as inactive protoxins and undergo posttranslational acylation on ε-amino groups of two internal conserved lysine residues by co-expressed toxin-activating acyltransferases. Here, we investigated how the chemical nature, position, and number of bound acyl chains govern the activities of Bordetella pertussis adenylate cyclase toxin (CyaA), Escherichia coli α-hemolysin (HlyA), and Kingella kingae cytotoxin (RtxA). We found that the three protoxins are acylated in the same E. coli cell background by each of the CyaC, HlyC, and RtxC acyltransferases. We also noted that the acyltransferase selects from the bacterial pool of acyl–acyl carrier proteins (ACPs) an acyl chain of a specific length for covalent linkage to the protoxin. The acyltransferase also selects whether both or only one of two conserved lysine residues of the protoxin will be posttranslationally acylated. Functional assays revealed that RtxA has to be modified by 14-carbon fatty acyl chains to be biologically active, that HlyA remains active also when modified by 16-carbon acyl chains, and that CyaA is activated exclusively by 16-carbon acyl chains. These results suggest that the RTX toxin molecules are structurally adapted to the length of the acyl chains used for modification of their acylated lysine residue in the second, more conserved acylation site.

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Cellular Lipid Composition Affects Sensitivity of Plant Pathogens to Fengycin, an Antifungal Compound Produced by Bacillus subtilis Strain CU12

Phytopathology ◽

10.1094/phyto-12-13-0336-r ◽

2014 ◽

Vol 104 (10) ◽

pp. 1036-1041 ◽

Cited By ~ 26

Author(s):

Cody Wise ◽

Justin Falardeau ◽

Ingrid Hagberg ◽

Tyler J. Avis

Keyword(s):

Bacillus Subtilis ◽

Lipid Composition ◽

Plant Pathogens ◽

Membrane Lipids ◽

Acyl Chain ◽

Fatty Acyl ◽

Subtilis Strain ◽

Antifungal Compound ◽

Membrane Pore ◽

Ergosterol Content

Fengycin is an antimicrobial cyclic lipopeptide produced by various Bacillus subtilis strains, including strain CU12. Direct effects of fengycin include membrane pore formation and efflux of cellular contents leading to cell death in sensitive microorganisms. In this study, four plant pathogens were studied in order to elucidate the role of membrane lipids in their relative sensitivity to fengycin. Inhibition of mycelial growth in these pathogens varied considerably. Analysis of membrane lipids in these microorganisms indicated that sensitivity correlated with low ergosterol content and shorter phospholipid fatty acyl chains. Sensitivity to fengycin also correlated with a lower anionic/zwitterionic phospholipid ratio. Our data suggest that decreased fluidity buffering capacity, as a result of low ergosterol content, and higher intrinsic fluidity afforded by short fatty acyl chain length may increase the sensitivity of microbial membranes to fengycin. Our results also suggest that lower content in anionic phospholipids may increase fengycin insertion into the membrane through reduced electrostatic repulsion with the negatively charged fengycin. The intrinsic membrane lipid composition may contribute, in part, to the observed level of antimicrobial activity of fengycin in various plant pathogens.

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Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1522071113 ◽

2016 ◽

Vol 113 (21) ◽

pp. 5928-5933 ◽

Cited By ~ 24

Author(s):

Stefka D. Spassieva ◽

Xiaojie Ji ◽

Ye Liu ◽

Kenneth Gable ◽

Jacek Bielawski ◽

...

Keyword(s):

Acyl Chain ◽

Strong Association ◽

Ectopic Expression ◽

Fatty Acyl ◽

Chemical Diversity ◽

Fatty Acyl Chain ◽

Length Variation ◽

Ceramide Synthase ◽

Hydrophobic Moiety

Sphingolipids exhibit extreme functional and chemical diversity that is in part determined by their hydrophobic moiety, ceramide. In mammals, the fatty acyl chain length variation of ceramides is determined by six (dihydro)ceramide synthase (CerS) isoforms. Previously, we and others showed that mutations in the major neuron-specific CerS1, which synthesizes 18-carbon fatty acyl (C18) ceramide, cause elevation of long-chain base (LCB) substrates and decrease in C18 ceramide and derivatives in the brain, leading to neurodegeneration in mice and myoclonus epilepsy with dementia in humans. Whether LCB elevation or C18 ceramide reduction leads to neurodegeneration is unclear. Here, we ectopically expressed CerS2, a nonneuronal CerS producing C22–C24 ceramides, in neurons of Cers1-deficient mice. Surprisingly, the Cers1 mutant pathology was almost completely suppressed. Because CerS2 cannot replenish C18 ceramide, the rescue is likely a result of LCB reduction. Consistent with this hypothesis, we found that only LCBs, the substrates common for all of the CerS isoforms, but not ceramides and complex sphingolipids, were restored to the wild-type levels in the Cers2-rescued Cers1 mutant mouse brains. Furthermore, LCBs induced neurite fragmentation in cultured neurons at concentrations corresponding to the elevated levels in the CerS1-deficient brain. The strong association of LCB levels with neuronal survival both in vivo and in vitro suggests high-level accumulation of LCBs is a possible underlying cause of the CerS1 deficiency-induced neuronal death.

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