Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies.
View Article and Find Full Text PDFThe rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.
View Article and Find Full Text PDFmicrobeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.
View Article and Find Full Text PDFJ Mass Spectrom Adv Clin Lab
November 2023
Pipettes are essential tools for biomedical and analytical laboratories, analogous to workstations for computer scientists. Variation in pipetting is a known unknown, as it is generally accepted that variations exist, but thus far, there have been limited studies on the extent of these variations in practice. In this mini-review, we highlight how manual pipetting is a key technique in the laboratory, and, although simple, inaccuracy and imprecision exist.
View Article and Find Full Text PDFWith the global emergence of drug-resistant bacteria causing difficult-to-treat infections, there is an urgent need for a tool to facilitate studies on key virulence and antimicrobial resistant factors. Mass spectrometry (MS) has contributed substantially to the elucidation of the structure-function relationships of lipid A, the endotoxic component of lipopolysaccharide which also serves as an important protective barrier against antimicrobials. Here, we present LipidA-IDER, an automated structure annotation tool for system-level scale identification of lipid A from high-resolution tandem mass spectrometry (MS) data.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2021
Many pathogenic bacteria are encased in a layer of capsular polysaccharide (CPS). This layer is important for virulence by masking surface antigens, preventing opsonophagocytosis, and avoiding mucus entrapment. The bacterial tyrosine kinase (BY-kinase) regulates capsule synthesis and helps bacterial pathogens to survive different host niches.
View Article and Find Full Text PDFMicrobiol Resour Announc
July 2021
Here, we report the genome sequence of Enterobacter hormaechei subsp. strain BEI01, originally deposited as a member of the Enterobacter cloacae complex. The genome is 4,900,246 bp in size with a GC content of 55.
View Article and Find Full Text PDFLipids play critical roles in developmental processes, and alterations in lipid metabolism are linked to a wide range of human diseases, including neurodegeneration, cancer, metabolic diseases, and microbial infections. Drosophila melanogaster, more commonly known as the fruit fly, is a powerful organism for developmental biology and human disease research. We have previously developed a comprehensive biochemical tool, based on liquid chromatography-mass spectrometry (LC-MS), to probe the dynamics of lipid remodeling during D.
View Article and Find Full Text PDFThe immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear.
View Article and Find Full Text PDFAzoles such as posaconazole (Posa) are highly potent against . However, when tested in chronic Chagas disease patients, a high rate of relapse after Posa treatment was observed. It appears that inhibition of cytochrome CYP51, the target of azoles, does not deliver sterile cure in monotherapy.
View Article and Find Full Text PDF(), the causative agent of tuberculosis (TB), is a highly successful intracellular pathogen with the ability to withstand harsh conditions and reside long-term within its host. In the dormant and persistent states, the bacterium tunes its metabolism and is able to resist the actions of antibiotics. One of the main strategies adopts is through its metabolic versatility-it is able to cometabolize a variety of essential nutrients and direct these nutrients simultaneously to multiple metabolic pathways to facilitate the infection of the host.
View Article and Find Full Text PDFThe outer membrane (OM) is an essential component of the Gram-negative bacterial envelope that protects the cells against external threats. To maintain a functional OM, cells require distinct mechanisms to ensure balance of proteins and lipids in the membrane. Mutations in OM biogenesis and/or homeostasis pathways often result in permeability defects, but how molecular changes in the OM affect barrier function is unclear.
View Article and Find Full Text PDFAltered lipid metabolism in macrophages is associated with various important inflammatory conditions. Although lipid metabolism is an important target for therapeutic intervention, the metabolic requirement involved in lipid accumulation during pro-inflammatory activation of macrophages remains incompletely characterized. We show here that macrophage activation with IFNγ results in increased aerobic glycolysis, iNOS-dependent inhibition of respiration, and accumulation of triacylglycerol.
View Article and Find Full Text PDFAntimicrob Agents Chemother
April 2018
Combinatorial chemotherapy is necessary for the treatment of malaria. However, finding a suitable partner drug for a new candidate is challenging. Here we develop an algorithm that identifies all of the gene pairs of that possess orthologues in yeast that have a synthetic lethal interaction but are absent in humans.
View Article and Find Full Text PDFMacrophages are professional phagocytes at the front line of immune defenses against foreign bodies and microbial pathogens. Various bacteria, which are responsible for deadly diseases including tuberculosis and salmonellosis, are capable of hijacking this important immune cell type and thrive intracellularly, either in the cytoplasm or in specialized vacuoles. Tight regulation of cellular metabolism is critical in shaping the macrophage polarization states and immune functions.
View Article and Find Full Text PDFTrypanosomatids are parasitic protozoa which cause a spectrum of diseases, including trypanosomiasis and leishmaniasis, affecting millions of humans and animals worldwide. The surface of most protozoan parasites is heavily decorated with lipids and lipid-anchored molecules, forming protective barriers and acting as virulence factors during infection. Sphingolipids (SP) are major components of eukaryotic biomembranes, which play important roles in structural integrity, energy homeostasis and signaling.
View Article and Find Full Text PDFGuang Pu Xue Yu Guang Pu Fen Xi
January 2017
In order to find out the constitute forms of lavenderessential oil-β-cyclodextrin inclusion complex and the process of release of lavenderessential oilwith temperature changes, we used Fourier transform infrared spectroscopy (FTIR) method to compare and analyze lavender essential oil (LO), β- cyclodextrin (β-CD) and lavender essential oil microcapsule (LOM), while the infrared spectral changes of release process at different temperatures of the oil in microcapsulewas analyzed, andthe principal component method was further used to explore the physical and chemical stability and release process of LO after it was entrapped by β-CD. The results showed that comparative analysis by infrared spectroscopy, characteristic peaks of LO embedded had redshift peak and its peak shape became wider, which mainly affected by the formation of molecular hydrogen bonds , p-π conjugate phenomenon and the spatial structure of β-CD; in addition, we set temperature range from 25 to 95 ℃, the temperature interval of 10 ℃, and then determined LOM by IR spectrum to test and verify physical and chemical stability and release conditions of LO which was embedded by β-CD. The results demonstrated that, water molecule inLOM hydrate was easily lost and the essential oil component of LOM was in stable physical and chemical properties, and the amount of escaping for LO at 95 ℃ was less than 6.
View Article and Find Full Text PDFBiochim Biophys Acta
January 2016
Diseases including tuberculosis and leprosy are caused by species of the Mycobacterium genus and are a huge burden on global health, aggravated by the emergence of drug resistant strains. Mycobacteria have a high lipid content and complex lipid profile including several unique classes of lipid. Recent years have seen a growth in research focused on lipid structures, metabolism and biological functions driven by advances in mass spectrometry techniques and instrumentation, particularly the use of electrospray ionization.
View Article and Find Full Text PDFImport and assembly of mitochondrial proteins depend on a complex interplay of proteinaceous translocation machineries. The role of lipids in this process has been studied only marginally and so far no direct role for a specific lipid in mitochondrial protein biogenesis has been shown. Here we analyzed a potential role of phosphatidic acid (PA) in biogenesis of mitochondrial proteins in Saccharomyces cerevisiae.
View Article and Find Full Text PDFDuring cell entry, non-enveloped viruses undergo partial uncoating to expose membrane lytic proteins for gaining access to the cytoplasm. We report that adenovirus uses membrane piercing to induce and hijack cellular wound removal processes that facilitate further membrane disruption and infection. Incoming adenovirus stimulates calcium influx and lysosomal exocytosis, a membrane repair mechanism resulting in release of acid sphingomyelinase (ASMase) and degradation of sphingomyelin to ceramide lipids in the plasma membrane.
View Article and Find Full Text PDFCurrently available drugs for Chagas' disease are limited by toxicity and low efficacy in the chronic stage. Posaconazole, the most advanced new anti-chagasic drug candidate, did not fully confirm its initial potential in a Phase II clinical trial for chronic Chagas' disease. Given that posaconazole is highly active against Trypanosoma cruzi in vitro, and was very well tolerated in clinical trials, it should not be abandoned.
View Article and Find Full Text PDFMycolic acids (MAs) are α-alkyl, β-hydroxy long-chain fatty acids found in abundance in the cell envelope of the Mycobacterium tuberculosis complex (MTBC). MAs form an efficient permeability barrier, modulate host innate immune responses, and are the targets of several anti-tuberculosis drugs. Using mass spectrometry, we measured the relative abundance of 80 MA species across 36 clinical isolates of MTBC covering four major phylogenetic lineages.
View Article and Find Full Text PDFInfluenza virus acquires a host-derived lipid envelope during budding, yet a convergent view on the role of host lipid metabolism during infection is lacking. Using a mass spectrometry-based lipidomics approach, we provide a systems-scale perspective on membrane lipid dynamics of infected human lung epithelial cells and purified influenza virions. We reveal enrichment of the minor peroxisome-derived ether-linked phosphatidylcholines relative to bulk ester-linked phosphatidylcholines in virions as a unique pathogenicity-dependent signature for influenza not found in other enveloped viruses.
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