Membrane Fatty Acid Research Articles

Differential reaction norms to ocean acidification in two oyster species from contrasting habitats.

Ocean acidification (OA), a consequence of the increase in anthropogenic emissions of carbon dioxide, causes major changes in the chemistry of carbonates in the ocean with deleterious effects on calcifying organisms. The pH/PCO2 range to which species are exposed in nature is important to consider when interpreting the response of coastal organisms to OA. In this context, emerging approaches, which assess the reaction norms of organisms to a wide pH gradient, are improving our understanding of tolerance thresholds and acclimation potential to OA. In this study, we deciphered the reaction norms of two oyster species living in contrasting habitats: the intertidal oyster Crassostrea gigas and the subtidal flat oyster Ostrea edulis, which are two economically and ecologically valuable species in temperate ecosystems. Six-month-old oysters of each species were exposed in common garden tanks for 48 days to a pH gradient ranging from 7.7 to 6.4 (total scale). Both species were tolerant down to a pH of 6.6 with high plasticity in fitness-related traits such as survival and growth. However, oysters underwent remodelling of membrane fatty acids to cope with decreasing pH along with shell bleaching impairing shell integrity and consequently animal fitness. Finally, our work revealed species-specific physiological responses and highlights that intertidal C. gigas seem to have a better acclimation potential to rapid and extreme OA changes than O. edulis. Overall, our study provides important data about the phenotypic plasticity and its limits in two oyster species, which is essential for assessing the challenges posed to marine organisms by OA.

Leukaemia Exposure Alters the Transcriptional Profile and Function of Macrophages in the Bone Marrow Niche

These authors contributed equally to this work: Martha M. Zarou & Amy Dawson Macrophages are fundamental cells of the innate immune system. Bone marrow (BM) resident macrophages are involved in antigen presentation, phagocytosis, efferocytosis (clearing of apoptotic cells) and play a critical role in regulating haematopoietic stem cell (HSC) function. In chronic myeloid leukaemia (CML), the disease-initiating leukaemic stem cells (LSCs) modulate the BM microenvironment to support leukaemia maintenance and progression. However, whether the CML BM niche alters the function of macrophages remains unknown. Using single-cell RNA sequencing (scRNA-seq) of human BM mononuclear cells, we demonstrate heterogeneity of tissue resident macrophages, isolated from CML patients at diagnosis, which cluster separately from BM macrophages deriving from heathy individuals. As most BM macrophages at diagnosis express BCR::ABL1 and are sensitive to TKI treatment, we further investigated if Philadelphia chromosome negative (Ph -) macrophages play a major role in CML development. We applied a chimeric CML mouse model (SCLtTA/BCR::ABL1) and reveal that temporal depletion of macrophages prior to leukaemia induction (using CSF1R antagonist antibody), increases leukaemia burden and decreases survival of chimeric mice following BCR::ABL1 induction (p<0.05). Comparison of CML exposed Ph - BM macrophages to control counterparts by scRNA-seq demonstrates that the CML niche drives two unique subpopulations of immature and anti-inflammatory macrophages. Functionally, we discover that Ph - BM macrophages exposed to a CML microenvironment display reduced phagocytic and efferocytic capacity, which correlates with reduction in mitochondrial respiration (p<0.05). Mechanistically, we show that diminished efferocytosis is mediated by reduced expression of the plasma membrane fatty acid translocase CD36. Additionally, treatment of primary mouse and human BM derived macrophages (BMDM) with the irreversible CD36 inhibitor sulfosuccinimidyl oleate (SSO), or genetic deletion of CD36 in THP-1 derived macrophages, results in reduced clearance of apoptotic cells in vitro. Furthermore, CD36 deficient macrophages display decreased mitochondrial respiration, similarly to CML exposed Ph - BMDM. Through untargeted liquid chromatography-mass spectrometry approach we identified the immunomodulatory protein lactotransferrin (LTF) as differentially secreted protein by leukaemic mouse stem/progenitor cells, when compared with secretome of normal counterparts (p<0.05). Treatment with LTF replicates the effect of CML exposure on BMDM, including decreased phagocytic function of mouse BMDM and THP-1 derived macrophages (p<0.05). Furthermore, mouse/human BMDM display reduced clearance of CML apoptotic cells following LTF exposure. Notably, LTF treatment reduces CD36 transcript and protein levels on BMDM and/or THP-1 derived macrophages, which correlates with reduced oxygen consumption rate and a 40% decrease in expression of the monocytic marker CD11b during macrophage differentiation, suggesting that secreted LTF is a major contributor to the immature phenotype of CML exposed macrophages. Overall, we present novel findings that dysregulated CML microenvironment modifies BM macrophage function, including their phagocytic and efferocytic capacity. This is at least partially contributed by secretion of LTF from CML stem/progenitor cells and modulation of CD36 expression on altered BM macrophages.

Abstract 12411: Fatty Acid Saturation Status in Murine High Fat Diets Modulates Platelet Reactivity

Introduction: We have recently shown that membrane fatty acids are key modulators of megakaryocyte differentiation and platelet formation. In obesity, patients have an altered plasma lipid composition, which coincides with enhanced platelet responsiveness to activation. However, the mechanism underlying this platelet phenotype remains unknown. Hypothesis: We hypothesized that the obese plasma lipidome alters the composition of the megakaryocyte membrane, which ultimately leads to the generation of hyper-reactive platelets. Aim: To investigate the impact of high fat diets with different fatty acid compositions on megakaryocyte development and platelet reactivity. Results: Mice were fed chow or high fat diets enriched in either saturated fatty acids (50% SFAs) or polyunsaturated fatty acids (50% PUFAs, omega-6-enriched). Neither high fat diet resulted in changes in megakaryocyte numbers, but both caused a significant increase in the size of bone marrow megakaryocytes, suggesting diet-derived lipid uptake into megakaryocytes. When examining platelet reactivity, we found that mice fed the SFA-enriched high fat diet exhibited increased expression of the active form of integrin αIIbβ3 (JON/A) in resting platelets and that both JON/A and P-selectin expression were significantly decreased after platelets were stimulated with ADP and the thromboxane A 2 analogue U46619. In contrast, platelets from mice fed the PUFA omega-6-enriched high fat diet had no differences in platelet reactivity compared to mice fed normal chow. Conclusions: Our data reveal that dietary fatty acid saturation status affects platelet reactivity, consistent with previous human studies showing variability in platelet reactivity in obese individuals. Further explorations will elucidate if plasma and/or platelet lipid content may be an indicator of risk for thrombosis or cardiovascular disease.

Features of the fatty acid profile of erythrocyte membranes in patients with fatty liver disease of alcoholic genesis

Introduction. Alcoholic steatosis, which is a reversible condition, is currently considered a significant risk factor for the progression of diffuse liver pathology, therefore understanding of its mechanisms at the molecular level is essential.Aim. To study the features of the fatty acid profile of erythrocyte membranes in patients with fatty liver disease of alcoholic origin for possible use of fatty acids (FAs) as biomarkers and potential therapeutic targets.Materials and methods. A total of 31 men with alcoholic fatty liver disease (AFLD) (average age of 45.1 ± 17.1 years) and 28 men of comparable age without AFLD and symptomatic pathology of internal organs were examined. The FA composition and levels of erythrocyte membranes (ER) were studied using Agilent 7000B (USA) triple quadrupole gas chromatography/mass spectrometry.Results and discussion. A higher level of a range of saturated FAs (lauric, margaric, pentadecane), monounsaturated FAs (MUFAs), which are additional factors for the progression of AFLD (palmitoleic, total monounsaturated acids), n-6/n-3 polyun-saturated FAs ratio (PUFAs), alpha-linolenic FA was detected in patients with AFL vs the control group (p = 0.00002–0.05). In contrast, the levels of arachidic and docosahexaenoic acids, total eicosapentaenoic and docosahexaenoic n-3 PUFAs, and total n-3 PUFAs were lower in patients with AFLD than in healthy men (p = 0.003–0.01), which is associated with increased ethanol induced adipose tissue lipolysis via PDE3B-AMPK axis. The use of FAs panel (C16:1;9, sum MUFA, n-6/n-3 PUFA, C22:6n3, C20:0) to distinguish patients with AFLD from healthy ones ensured high levels of sensitivity (79%), and specificity (81%) (AUC 0.808). Multidirectional associations of FA levels in erythrocyte membranes with each other and liver tests and lipid profile results were revealed.Conclusion. Thus, the features of erythrocytes membrane FAs in patients with AFLD and the potential to use them as biomarkers for differentiation of people with AFLD from healthy individuals have been identified.

Disinfectant sodium dichloroisocyanurate synergistically strengthened sludge acidogenic process and pathogens inactivation: Targeted upregulation of functional microorganisms and metabolic traits via self-adaptation

Harmless and resourceful treatment of waste activated sludge (WAS) have been the crucial goal for building environmental-friendly and sustainable society, while the synergistic realization approach is currently limited. This work skillfully utilized the disinfectant sodium dichloroisocyanurate (NaDCC) to simultaneously achieve the pathogenic potential inactivation (decreased by 60.1 %) and efficient volatile fatty acids (VFAs) recovery (increased by 221.9 %) during WAS anaerobic fermentation in rather cost-effective way (Chemicals costs:0.4 USD/kg VFAs versus products benefits: 2.68 USD/kg chemical). Mechanistic analysis revealed that the C=O and NCl bonds in NaDCC could spontaneously absorb sludge (binding energy -4.9 kJ/mol), and then caused the sludge disintegration and organic substrates release for microbial utilization due to the oxidizability of NaDCC. The disruption of sludge structure along with the increase of bioavailable fermentation substrates contributed to the selectively regulation of microbial community via enriching VFAs-forming microorganisms (e.g., Pseudomonas and Streptomyces) and reducing VFAs-consuming microorganisms, especially aceticlastic methanogens (e.g., Methanothrix and Methanospirillum). Correspondingly, the metabolic functions of membrane transport, substrate metabolism, pyruvate metabolism, and fatty acid biosynthesis locating in the central pathway of VFAs production were all upregulated while the methanogenic step was inhibited (especially acetate-type methanogenic pathway). Further exploration unveiled that for those enriched functional anaerobes were capable to activate the self-adaptive systems of DNA replication, SOS response, oxidative stress defense, efflux pump, and energy metabolism to counteract the unfavorable NaDCC stress and maintain high microbial activities for efficient VFAs yields. This study would provide a novel strategy for synergistic realization of harmless and resourceful treatment of WAS, and identify the interrelations between microbial metabolic regulations and adaptive responses.

Acyl-AcpB, a FabT corepressor in Streptococcus pyogenes.

Membranes are a universal barrier to all cells. Phospholipids, essential bacterial membrane components, are composed of a polar head and apolar fatty acid (FA) chains. Most bacterial FAs are synthesized by the Type II FA synthesis pathway (FASII). In Streptococcaceae, Enterococci, and Lactococcus lactis, a unique feedback mechanism controls the FASII gene expression. FabT, encoded in the FASII main locus, is the repressor, and it is activated by long-chain acyl-acyl carrier protein (acyl-ACP). Many Streptococci, Enterococcus faecalis, but not L. lactis, possess two ACPs. The AcpA-encoding gene is within the FASII locus and is coregulated with the FASII genes. Acyl-AcpA is the end product of FASII. The AcpB-encoding gene is in operon with plsX encoding an acyl-ACP:phosphate acyltransferase. The role of acyl-AcpB as FabT corepressor is controversial. Streptococcus pyogenes, which causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections, possesses AcpB. In this study, by comparing the expression of FabT-controlled genes in an acpB-deleted mutant with those in a wild-type and in a fabT mutant strain, grown in the presence or absence of exogenous FAs, we show that AcpB is the S. pyogenes FabT main corepressor. Its deletion impacts membrane FA composition and bacterial adhesion to eucaryotic cells, highlighting the importance of FASII control. Importance Membrane composition is crucial for bacterial growth or interaction with the environment. Bacteria synthesize fatty acids (FAs), membrane major constituents, via the Type II FAS (FASII) pathway. Streptococci control the expression of the FASII genes via a transcriptional repressor, FabT, with acyl-acyl carrier proteins (ACPs) as corepressor. Streptococcus pyogenes that causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections possesses two ACPs. acpA, but not acpB, is a FASII gene. In this study, we show that acyl-AcpBs are FabT main corepressors. Also, AcpB deletion has consequences on the membrane FA composition and bacterial adhesion to host cells. In addition to highlighting the importance of FASII control in the presence of exogeneous FAs for the adaptation of bacteria to their environment, our data indicate that FASII gene repression is mediated by a corepressor whose gene expression is not repressed in the presence of exogenous FAs.

Fungi under Modified Atmosphere-The Effects of CO2 Stress on Cell Membranes and Description of New Yeast Stenotrophomyces fumitolerans gen. nov., sp. nov.

High levels of carbon dioxide are known to inhibit the growth of microorganisms. A total of twenty strains of filamentous fungi and yeasts were isolated from habitats with enriched carbon dioxide concentration. Most strains were derived from modified atmosphere packed (MAP) food products or mofettes and were cultivated under an atmosphere of 20% CO2 and 80% O2. The influence of CO2 on fungal cell membrane fatty acid profiles was examined in this study. Major changes were the increase in linolenic acid (C18:3 cis 9, 12, 15) and, additionally in most strains, linoleic acid (C18:2 cis 9, 12) with a maximum of 24.8%, at the expense of oleic (C18:1 cis 9), palmitic (C16:0), palmitoleic (C16:1 cis 9) and stearic acid (C18:0). The degree of fatty acid unsaturation increased for all of the strains in the study, which consequently led to lower melting temperatures of the cell membranes after incubation with elevated levels of CO2, indicating fluidization of the membrane and a potential membrane malfunction. Growth was reduced in 18 out of 20 strains in laboratory experiments and a change in pigmentation was observed in several strains. Two of the isolated strains, strain WT5 and strain WR1, were found to represent a hitherto undescribed yeast for which the new genus and species Stenotrophomyces fumitolerans (MB# 849906) is proposed.

Implication of Mn-cofactored superoxide dismutase in the tolerance of swarmer Pseudomonas aeruginosa to polymixin, ciprofloxacin and meropenem antibiotics.

The protective role of superoxide dismutase (Sod) against oxidative stress, resulting from the common antibiotic pathway of action, has been studied in the wild type and mutant strains of swarmer Pseudomonas aeruginosa, lacking Cytosolic Mn-Sod (sodM), Fe-Sod (sodB) or both Sods (sodMB).Our results showed that inactivation of sodB genes leads to significant motility defects and tolerance to meropenem. This resistance is correlated with a greater membrane unsaturation as well as an effective intervention of Mn-Sod isoform, in antibiotic tolerance.Moreover, loss of Mn-Sod in sodM mutant, leads to polymixin intolerance and is correlated with membrane unsaturation. Effectivelty, sodM mutant showed an enhanced swarming motility and a conserved rhamnolipid production. Whereas, in the double mutant sodMB, ciprofloxacin tolerance would be linked to an increase in the percentage of saturated fatty acids in the membrane, even in the absence of superoxide dismutase activity.The overall results showed that Mn-Sod has a protective role in the tolerance to antibiotics, in swarmer P.aeruginosa strain. It has been further shown that Sod intervention in antibiotic tolerance is through change in membrane fatty acid composition.

Alterations in plasma and erythrocyte membrane fatty acid composition following exposure to toxic copper level affect membrane deformability and fluidity in female wistar rats

BackgroundDeformability and fluidity function of the red blood cell membrane are properties defined by the lipid composition. Toxic copper level induces membrane lipid peroxidation which could cause membrane instability. This study therefore investigated the effect of exposure to toxic copper level for 30 days on red blood cell membrane deformability and fluidity in female Wistar rats. MethodsTwelve (12) female Wistar rats (160 ± 10 g) were randomly grouped (n = 6) into control (given 0.1 ml distilled water p.o.) and copper-toxic (100 mg/kg Copper Sulphate, p.o.), and treated for 30 days. Plasma obtained and RBC membrane prepared from blood collected over EDTA post-treatment were assayed for total cholesterol (TC), phospholipids and fatty acid profile using spectrophotometry and Gas chromatography while heparinized blood was subjected to fragility test. Data were analyzed using student T-test for statistical significance at p < 0.05. Results and conclusionPlasma TC increased by 4.33% while RBC membrane TC decreased by 20.32% in copper-toxic group compared to control. Compared to control, excess copper significantly increased membrane phospholipids level (0.72 ± 0.01 vs 0.59 ± 0.04 mg/dL) but reduced membrane cholesterol/phospholipid ratio (46.61 ± 4.72 vs 72.66 ± 6.47) and stability (by 23.53%). Number of cis- and saturated fatty acids increased in copper-treated plasma and RBC membrane compared to control. Exposure to toxic copper level alters erythrocyte membrane fluidity and deformability by disrupting membrane lipid composition, saturation, bond configuration in phospholipids and permeability.

Supply of palmitic, stearic, and oleic acid changes rumen fiber digestibility and microbial composition

The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent interest in the dietary fatty acid profile to dairy cows enlightened the possible beneficial effect of specific fatty acids (e.g., palmitic, stearic, and oleic acids) on total-tract fiber digestibility. Because palmitic, stearic, and oleic acids are the main fatty acids present in ruminal bacterial cells, we hypothesize that the dietary supply of these fatty acids will favor their incorporation into the bacterial cell membranes, which will support the growth and enrichment of fiber-digesting bacteria in the rumen. Our objective in this experiment was to investigate how dietary supply of palmitic, stearic, and oleic acid affect fiber digestion, bacterial membrane fatty acid profile, microbial growth, and composition of the rumen bacterial community. Diets were randomly assigned to 8 single-flow continuous culture fermenters arranged in a replicated 4 × 4 Latin square with four 11-d experimental periods. Treatments were (1) a control basal diet without supplemental fatty acids (CON); (2) the control diet plus palmitic acid (PA); (3) the control diet plus stearic acid (SA); and (4) the control diet plus oleic acid (OA). All fatty acid treatments were included in the diet at 1.5% of the diet (dry matter [DM] basis). The basal diet contained 50% orchardgrass hay and 50% concentrate (DM basis) and was supplied at a rate of 60 g of DM/d in 2 equal daily offers (0800 and 1600 h). Data were analyzed using a mixed model considering treatments as fixed effect and period and fermenter as random effects. Our results indicate that PA increased in vitro fiber digestibility by 6 percentage units compared with the CON, while SA had no effect and OA decreased fiber digestibility by 8 percentage units. Oleic acid decreased protein expression of the enzymes acetyl-CoA carboxylase compared with CON and PA, while fatty acid synthase was reduced by PA, SA, and OA. We observed that PA, but not SA or OA, altered the bacterial community composition by enhancing bacterial groups responsible for fiber digestion. Although the dietary fatty acids did not affect the total lipid content and the phospholipid fraction in the bacterial cell, PA increased the flow of anteiso C13:0 and anteiso C15:0 in the phospholipidic membrane compared to the other treatments. In addition, OA increased the flow of C18:1 cis-9 and decreased C18:2 cis-9,cis-12 in the bacterial phospholipidic membranes compared to the other treatments. Palmitic acid tended to increase bacterial growth compared to other treatments, whereas SA and OA did not affect bacterial growth compared with CON. To our knowledge, this is the first research providing evidence that palmitic acid supports ruminal fiber digestion through shifts in bacterial fatty acid metabolism that result in changes in growth and abundance of fiber-degrading bacteria in the microbial community.

Gut microbiota regulation of inflammatory cytokines and microRNAs in diabetes-associated cognitive dysfunction.

Type 2 diabetes mellitus (T2DM) has a major comorbidity known as diabetes-associated cognitive dysfunction (DACD). Studies have demonstrated that the gut microbiota is crucial in mediating the cognitive abnormalities that occur in diabetic individuals. Additionally, changes in dietary fatty acid intake levels, inflammatory cytokines, and microRNAs (miRs) have an effect on cognitive performance. However, further studies are needed to identify the link between gut microbiota and cognition in T2DM patients and the role that the above indicators play in this process. In order to provide a new rationale for the treatment of cognitive dysfunction in diabetes, this study was conducted in the middle-aged and elderly Beijing population to examine the differences in gut microbiota between DACD and T2DM patients as well as to further explore the role of erythrocyte membrane fatty acids, inflammatory cytokines, and miRs in gut microbiota-mediated cognitive impairment. According to the results, the abundance of norank_f_Eubacterium_coprostanoligenes_group, Acidaminococcus, Enterorhabdus, and norank_f_Clostridium_methylpentosum_group was higher in DACD patients compared to T2DM patients at the genus level. Compared with T2DM patients, plasma interleukin-12 (IL-12) concentrations were significantly higher in DACD patients than in T2DM patients, and IL-12 was significantly positively correlated with norank_f_Eubacterium_coprostanoligenes_group. In addition, plasma miR-142-5p was significantly positively correlated with Enterorhabdus and norank_f_Eubacterium_coprostanoligenes_group. We therefore hypothesize that cognitive impairment in T2DM patients is associated with altered gut microbial composition and that the effect of microbiota on cognition may be mediated through IL-12 and miR-142-5p. KEY POINTS: • Type 2 diabetes with or without cognitive impairment differs in gut microbiota. • Differential genera of gut microbiota were associated with inflammatory cytokines. • Differential genera of gut microbiota were associated with plasma microRNAs.

Phosphatase A1 accessory protein PlaS from Serratia marcescens controls cell membrane permeability, fluidity, hydrophobicity, and fatty acid composition in Escherichia coli BL21

Phospholipase A1 (PlaA) plays a pivotal role in diverse applications within the food and biochemical medical industries. Herein, we investigate the impact of the accessory protein encoded by plaS from Serratia marcescens on PlaA activity in Escherichia coli. Notably, PlaS demonstrates the ability to enhance PlaA activity while concurrently exhibiting inhibitory effects on the growth of E. coli BL21 (DE3). Our study revolves around probing the inhibitory action of PlaS on E. coli BL21 (DE3). PlaS exhibits a propensity to heighten both the permeability of outer and inner cell membranes, leading to concomitant reductions in membrane fluidity and surface hydrophobicity. This phenomenon is validated through scanning electron microscopy (SEM) analysis, which highlights PlaS's capacity to compromise membrane integrity. Moreover, through a comprehensive comparative transcriptomic sequencing approach, we identify four down-regulated genes (galM, ybhC, ldtC, and kdpB) alongside two up-regulated genes (rbsB and degP). These genes are intricately associated with processes such as cell membrane synthesis and modification, energy metabolism, and transmembrane transport. Our investigation unveils the intricate gene-level mechanisms underpinning PlaS-mediated growth inhibition and membrane disruption. Consequently, our findings serve as a significant reference for the elucidation of membrane protein mechanisms, shedding light on potential avenues for future exploration.

Unique and generic crossed metabolism in response to four sub-lethal environmental stresses in the oriental fruit fly, Bactrocera dorsalis Hendel

Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

Fatty Acids Profile and the Relevance of Membranes as the Target of Nutrition-Based Strategies in Atopic Dermatitis: A Narrative Review.

Recently, the prevalence of atopic dermatitis has increased drastically, especially in urban populations. This multifactorial skin disease is caused by complex interactions between various factors including genetics, environment, lifestyle, and diet. In eczema, apart from using an elimination diet, the adequate content of fatty acids from foods (saturated, monounsaturated, and polyunsaturated fatty acids) plays an important role as an immunomodulatory agent. Different aspects regarding atopic dermatitis include connections between lipid metabolism in atopic dermatitis, with the importance of the MUFA levels, as well as of the omega-6/omega-3 balance that affects the formation of long-chain (C20 eicosanoic and C22 docosaenoic) fatty acids and bioactive lipids from them (such as prostaglandins). Impair/repair of the functioning of epidermal barrier is influenced by these fatty acid levels. The purpose of this review is to drive attention to membrane fatty acid composition and its involvement as the target of fatty acid supplementation. The membrane-targeted strategy indicates the future direction for dermatological research regarding the use of nutritional synergies, in particular using red blood cell fatty acid profiles as a tool for checking the effects of supplementations to reach the target and influence the inflammatory/anti-inflammatory balance of lipid mediators. This knowledge gives the opportunity to develop personalized strategies to create a healthy balance by nutrition with an anti-inflammatory outcome in skin disorders.

Improved Membrane Permeability via Hypervesiculation for In Situ Recovery of Lycopene in Escherichia coli.

Lycopene biosynthesis is frequently hampered by downstream processing hugely due to its inability to be secreted out from the producing chassis. Engineering cell factories can resolve this issue by secreting this hydrophobic compound. A highly permeable E.coli strain was developed for a better release rate of lycopene. Specifically, the heterologous mevalonate pathway and crtEBI genes from Corynebacterium glutamicum were overexpressed in Escherichia coli BL21 (DE3) for lycopene synthesis. To ensure in situ lycopene production, murein lipoprotein, lipoprotein NlpI, inner membrane permease protein, and membrane-anchored protein in TolA-TolQ-TolR were deleted for improved membrane permeability. The final strain, LYC-8, produced 438.44 ± 8.11 and 136.94 ± 1.94 mg/L of extracellular and intracellular lycopene in fed-batch fermentation. Both proteomics and lipidomics analyses of secreted outer membrane vesicles were perfect indicators of hypervesiculation. Changes in the ratio of saturated fatty acids, unsaturated fatty acids, and cyclopropane fatty acids coupled with the branching and acyl chain lengths altered the membrane fatty acid composition. This ensured membrane fluidity and permeability for in situ lycopene release. The combinatorial deletion of these genes altered the cellular morphology. The structural and morphological changes in cell shape, size, and length were associated with changes in the mechanical strength of the cell envelope. The enhanced lycopene production and secretion mediated by improved membrane permeability established a cell lysis-free system for an efficient releasing rate and downstream processing, demonstrating the importance of vesicle-associated membrane permeability in efficient lycopene production.

Geometrical isomerization of arachidonic acid during lipid peroxidation interferes with ferroptosis.

Geometrical mono-trans isomers of arachidonic acid (mtAA) are endogenous products of free radical-induced cis-trans double bond isomerization occurring to natural fatty acids during cell metabolism, including lipid peroxidation (LPO). Very little is known about the functional roles of mtAA and in general on the effects of mono-trans isomers of polyunsaturated fatty acids (mtPUFA) in various types of programmed cell death, including ferroptosis. Using HT1080 and MEF cell cultures, supplemented with 20μM PUFA (i.e., AA, EPA or DHA) and their mtPUFA congeners, ferroptosis occurred in the presence of RSL3 (a direct inhibitor of glutathione peroxidase 4) only with the PUFA in their natural cis configuration, whereas mtPUFA showed an anti-ferroptotic effect. By performing the fatty acid-based membrane lipidome analyses, substantial differences emerged in the membrane fatty acid remodeling of the two different cell fates. In particular, during ferroptosis mtPUFA formation and their incorporation, together with the enrichment of SFA, occurred. This opens new perspectives in the role of the membrane composition for a ferroptotic outcome. While pre-treatment with AA promoted cell death for treatment with H2O2 and RSL3, mtAA did not. Cell death by AA supplementation was suppressed also in the presence of either ferroptosis inhibitors, such as the lipophilic antioxidant ferrostatin-1, or NADPH oxidase (NOX) inhibitors, including diphenyleneiodonium chloride and apocynin. Our results confirm a more complex scenario for ferroptosis than actually believed. While LPO processes are active, the importance of environmental lipid levels, balance among SFA, MUFA and PUFA in lipid pools and formation of mtPUFA influence the membrane phospholipid turnover, with crucial effects in the occurrence of cell death by ferroptosis.

The occurrence and resistance of Shigella flexneri CECT4804 to acid stress in vitro and in vivo.

The ability to maintain intra‑cellular pH is crucial for many microbes mainly the enterobacteria to survive in diverse environments, particularly those that undergo fluctuations in pH. In this context, the growth and survival of Shigella flexneri at different acid pH values were evaluated to explain the response strategies involved in the adaptation of S. flexneri CECT4804 in acid stress conditions. Furthermore, the capacity of this strain to produce slime on Congo Red Agar, biofilm formation on polystyrene plate and hydrophobicity are reported. In addition, the modification of the membrane fatty acids profiles has been studied. Moreover, an infection with the stressed strain was realized on rats in rates and examined for their toxicity in intestine tissue. The obtained results show that the strain survival is strongly influenced by acidity. Indeed, the stressed and unstressed strains became biofilm positive after acid stress. A significant increase in the hydrophobicity percentage compared to the values found under normal conditions, is also noticed. For the membrane fatty acids analysis, the acidity induces several modifications in the membrane composition. After the infection, the gravest lesion was registered in the intestine of rats administered with the bacteria stressed at the lowest pH.

Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.

Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

Shigella flexneri Adapts to Niche-Specific Stresses through Modifications in Cell Envelope Composition and Decoration.

Shigella flexneri is the primary causative agent of worldwide shigellosis. As the pathogen transverses the distinct niches of the gastrointestinal tract it necessitates dynamic adaptation strategies to mitigate host antimicrobials such as dietary fatty acids (FAs) and the bile salt, deoxycholate (DOC). This study investigates the dynamics of the S. flexneri cell envelope, by interrogating adaptations following FA or DOC exposure. We deciphered the effects of FAs and DOC on bacterial membrane fatty acid and lipopolysaccharide (LPS) compositions. We identified novel LPS-based strategies by the pathogen to support resistance to these host compounds. In particular, expression of S. flexneri very-long O antigen (VL-Oag) LPS was found to play a central role in stress mitigation, as VL-Oag protects against antimicrobial FAs, but its presence rendered S. flexneri susceptible to DOC stress. Collectively, this work underpins the importance for S. flexneri to maintain appropriate regulation of cell envelope constituents, in particular VL-Oag LPS, to adequately adapt to diverse stresses during infection.

Locally Enhanced Electric Field Treatment of E. coli: TEM, FT-IR and Raman Spectrometry Study

In this paper, we report the study of the low-voltage locally enhanced electric field treatment (LEEFT) of E. coli bacteria via TEM analysis and FT-IR and Raman spectrometry. The formation of pores was confirmed by TEM, which revealed the membrane rupture along with the formation of precipitates in the membrane and the cell volume, and by photoluminescence spectra of propidium iodide dye. LEEFT results in the alternation of DNA and RNA structure, indicated by the change in its α-helical and β-helical forms, decrease and narrowing of the nucleic acids-related IR and Raman peaks. Membrane damage is illustrated by the ambiguous character after low-voltage exposure: several membrane fatty acids’ peaks are broadening, while the others narrow, which indicates the overall change of the molecular bonds in their moiety, and may result from the rigidification during the shrinkage of the inner membrane and the increase in fluidity of the outer membrane. The corresponding fingerprints of cytochrome c and bo, located in the membrane or in the periplasm, on Raman spectra, reflect the arising changes in their structure and moiety. The observed changes were partially confirmed by TEM images, which indicate the dense precipitates’ formation in the cell volume and membrane, as well as the cytoplasmic membrane shrinkage away from the outer membrane.