Analysis of the Phospholipid Profile of the Collection Strain PAO1 and Clinical Isolates of Pseudomonas aeruginosa in Relation to Their Attachment Capacity

Bacteria form multicellular and resistant structures named biofilms. Biofilm formation starts with the attachment phase, and the molecular actors involved in this phase, except adhesins, are poorly characterized. There is growing evidence that phospholipids are more than simple structural bricks. They are involved in bacterial adaptive physiology, but little is known about their role in biofilm formation. Here, we report a mass spectrometry analysis of the phospholipid (PL) profile of several strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. The aim of our study was to evaluate a possible link between the PL profile of a strain and its attachment phenotype. Our results showed that PL profile is strongly strain-dependent. The PL profile of P. aeruginosa PAO1, a collection strain, was different from those of 10 clinical isolates characterized either by a very low or a very high attachment capacity. We observed also that the clinical strain’s PL profiles varied even more importantly between isolates. By comparing groups of strains having similar attachment capacities, we identified one PL, PE 18:1-18:1, as a potential molecular actor involved in attachment, the first step in biofilm formation. This PL represents a possible target in the fight against biofilms.     

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1^+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1^+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.     

KRAS,A Prime Mediator in Pancreatic Lipid Synthesis through Extra Mitochondrial Glutamine and Citrate Metabolism

Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven pancreatic cancer is very lethal, with a five-year survival rate of <9%, irrespective of therapeutic advances. Different treatment modalities including chemotherapy, radiotherapy, and immunotherapy demonstrated only marginal efficacies because of pancreatic tumor specificities. Surgery at the early stage of the disease remains the only curative option, although only in 20% of patients with early stage disease. Clinical trials targeting the main oncogenic driver, KRAS, have largely been unsuccessful. Recently, global metabolic reprogramming has been identified in patients with pancreatic cancer and oncogenic KRAS mouse models. The newly reprogrammed metabolic pathways and oncometabolites affect the tumorigenic environment. The development of methods modulating metabolic reprogramming in pancreatic cancer cells might constitute a new approach to its therapy. In this review, we describe the major metabolic pathways providing acetyl-CoA and NADPH essential to sustain lipid synthesis and cell proliferation in pancreatic cancer cells.     

The plasma phospholipidome of Tursiops truncatus: From physiological insight to the design of prospective tools for managed cetacean monitorization

Plasma biochemical analysis remains one of the established ways of monitoring captive marine mammal health. More recently, complementary plasma lipidomic analysis has proven to be a valid tool in disease diagnosis and prevention, with the potential to validate and complement common biochemical analysis, providing a more integrative approach. In this study, we thoroughly characterized the plasma polar lipid content of Tursiops truncatus, the most common cetacean species held under human care. Our results showed that phosphatidylcholine, lysophosphatidylcholine, and sphingomyelins (CerPCho) are the most represented phospholipid classes in T. truncatus plasma. Palmitic, oleic, and stearic acids are the major fatty acid (FA) present esterified to the plasma polar lipids of this species, although some n-3 species are also remarkably present, namely eicosapentaenoic and docosahexaenoic acids. The polar lipidome identified by HILIC LC–MS allowed identifying 304 different lipid species. These species belong to the phosphatidylcholine (103 lipid species), lysophosphatidylcholine (35), phosphatidylethanolamine (71), lysophosphatidylethanolamine (20), phosphatidylglycerol (13), lysophosphatidylglycerol (5), phosphatidylinositol (15), lysophosphatidylinositol (3), phosphatidylserine (6) lysophosphatidylserine (1), and sphimgomyelin (32) classes. This was the first time that the dolphin plasma phospholipid profile was characterized, providing a knowledge that will be important to further understand lipid metabolism and physiological regulation in small cetaceans. Furthermore, this study proved the practicability of the use of plasma lipid profiling for health assessment in marine mammals under human care.     

Characterization and Discrimination of Ancient Grains: A Metabolomics Approach

Hulled, or ancient, wheats were the earliest domesticated wheats by mankind and the ancestors of current wheats. Their cultivation drastically decreased during the 1960s; however, the increasing demand for a healthy and equilibrated diet led to rediscovering these grains. Our aim was to use a non-targeted metabolomic approach to discriminate and characterize similarities and differences between ancient Triticum varieties. For this purpose, 77 hulled wheat samples from three different varieties were collected: Garfagnana T. turgidum var. dicoccum L. (emmer), ID331 T. monococcum L. (einkorn) and Rouquin T. spelta L. (spelt). The ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-QTOF) metabolomics approach highlighted a pronounced sample clustering according to the wheat variety, with an excellent predictability (Q²), for all the models built. Fifteen metabolites were tentatively identified based on accurate masses, isotopic pattern, and product ion spectra. Among these, alkylresorcinols (ARs) were found to be significantly higher in spelt and emmer, showing different homologue composition. Furthermore, phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPC) levels were higher in einkorn variety. The results obtained in this study confirmed the importance of ARs as markers to distinguish between Triticum species and revealed their values as cultivar markers, being not affected by the environmental influences.     

Mass Spectrometry Methodology in Lipid Analysis

Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.     

Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.     

乳酸菌发酵过程发酵液脂肪酸组生态位的异质性

为探究乳酸菌发酵过程中发酵液脂肪酸组生态位的异质性,测定8 种乳酸菌发酵过程中乳酸菌活菌数和发酵液脂肪酸组,分析生态位宽度和重叠度与乳酸菌生长的关系。结果表明,不同乳酸菌生长能力差异显著,鼠李糖乳杆菌FJAT-13807生长能力最强,嗜热链球菌FJAT-43774最弱。8 种乳酸菌发酵液脂肪酸组共检测到91 条生物标记,其中直链脂肪酸12 条、支链脂肪酸70 条、未能分离的脂肪酸9 条,其含量顺序为直链脂肪酸＞支链脂肪酸＞未能分离的脂肪酸。不同乳酸菌发酵液脂肪酸总量差异显著（P＜0.05）,但乳酸菌发酵液脂肪酸总量与菌生长能力无直接相关性。发酵初期（1 h）,不同乳酸菌发酵液的脂肪酸生态位宽度差异不显著,菌株间脂肪酸生态位重叠程度较高,活菌数较低,环境容量较大,生态位宽度与重叠无相关性;发酵中期（24 h）,乳酸菌发酵液脂肪酸生态位宽度和重叠发生较大分化,影响处于对数生长期的乳酸菌生长模式,生态位宽度增加,乳酸菌生长速度下降,活菌数呈线性方程增长;生态位宽度减少,乳酸菌生长速度增加,活菌数呈抛物线方程增长;生态位宽度维持,乳酸菌生长速度维持原有方式;发酵后期（48 h）,乳酸菌发酵液脂肪酸生态位宽度与重叠也有类似分化,此时,乳酸菌处于稳定消亡期,生态位宽度较宽,乳酸菌生长能力下降,活菌数呈指数方程下降;生态位宽度较窄,乳酸菌生长能力增强,活菌数呈一元三次方程变动;生态位宽度维持,乳酸菌维持原有的规律,活菌数呈幂指数下降。乳酸菌发酵液脂肪酸生态位宽度和重叠的变化可用于乳酸菌生长势和资源利用率评估,为乳酸菌生长生态学研究提供新思路。