scholarly journals Phosphatidylcholine biosynthesis in Mitis group streptococci via host metabolite scavenging

2019 ◽  
Author(s):  
Luke R. Joyce ◽  
Ziqiang Guan ◽  
Kelli L. Palmer
Keyword(s):  
Membrane Lipids ◽  
Cellular Membrane ◽  
Human Pathogen ◽  
Opportunistic Pathogens ◽  
Membrane Biology ◽  
Host Interactions ◽  
Fundamental Information ◽  
Phosphatidylcholine Biosynthesis ◽  
Health And Disease ◽  
Mechanistic Basis

AbstractThe Mitis group streptococci include the major human pathogenStreptococcus pneumoniaeand the opportunistic pathogensS. mitisandS. oraliswhich are human oral cavity colonizers and agents of bacteremia and infective endocarditis in immunocompromised patients. Bacterial membrane lipids play crucial roles in microbe-host interactions, yet for many pathogens, the composition of the membrane is poorly understood. In this study, we characterized the lipidomes of selected species of Mitis group streptococci and investigated the mechanistic basis for biosynthesis of the phospholipid phosphatidylcholine (PC). PC is a major lipid in eukaryotic cellular membranes, but it is considered to be comparatively rare in bacterial taxa. Using liquid chromatography/mass spectrometry (LC/MS) in conjunction with stable isotope tracing, we determined that Mitis group streptococci synthesize PC via the rare host metabolite scavenging pathway, the glycerophosphocholine (GPC) pathway, which is largely uncharacterized in bacteria. Our work demonstrates that Mitis group streptococci includingS. pneumoniaeremodel their membrane in response to the major human metabolites GPC and lysoPC.ImportanceWe lack fundamental information about the composition of the cellular membrane even for the best studied pathogens of critical significance for human health. The Mitis group streptococci are closely linked to humans in health and disease, yet their membrane biology is poorly understood. Here, we demonstrate that these streptococci scavenge major human metabolites and use them to synthesize the membrane phospholipid phosphatidylcholine. Our work is significant because it identifies a mechanism by which the major human pathogenS. pneumoniaeand the primary human oral colonizersS. mitisandS. oralisremodel their membrane in response to host metabolites.

scholarly journals Phosphatidylcholine Biosynthesis in Mitis Group Streptococci via Host Metabolite Scavenging

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Luke R. Joyce ◽  
Ziqiang Guan ◽  
Kelli L. Palmer
Keyword(s):  
Membrane Lipids ◽  
Cellular Membrane ◽  
Human Pathogen ◽  
Content Type ◽  
Membrane Biology ◽  
Host Interactions ◽  
Fundamental Information ◽  
Phosphatidylcholine Biosynthesis ◽  
Health And Disease ◽  
Mechanistic Basis

ABSTRACT The mitis group streptococci include the major human pathogen Streptococcus pneumoniae and the opportunistic pathogens Streptococcus mitis and Streptococcus oralis, which are human oral cavity colonizers and agents of bacteremia and infective endocarditis in immunocompromised patients. Bacterial membrane lipids play crucial roles in microbe-host interactions; for many pathogens, however, the composition of the membrane is poorly understood. In this study, we characterized the lipidomes of selected species of mitis group streptococci and investigated the mechanistic basis for biosynthesis of the phospholipid phosphatidylcholine (PC). PC is a major lipid in eukaryotic cellular membranes, but it is considered to be comparatively rare in bacterial taxa. Using liquid chromatography-mass spectrometry in conjunction with stable isotope tracing, we determined that mitis group streptococci synthesize PC via a rare host-metabolite-scavenging pathway, the glycerophosphocholine (GPC) pathway, which is largely uncharacterized in bacteria. Our work demonstrates that mitis group streptococci, including S. pneumoniae, remodel their membranes in response to the major human metabolites GPC and lysophosphatidylcholine. IMPORTANCE We lack fundamental information about the composition of the cellular membrane even for the best-studied pathogens of critical significance for human health. The mitis group streptococci are closely linked to humans in health and disease, but their membrane biology is poorly understood. Here, we demonstrate that these streptococci scavenge major human metabolites and use them to synthesize the membrane phospholipid PC. Our work is significant because it identifies a mechanism by which the major human pathogen S. pneumoniae and the primary human oral colonizers S. mitis and S. oralis remodel their membranes in response to host metabolites.

The organization of cell surface membrane domains

1989 ◽  
Vol 47 ◽  
pp. 804-805
Author(s):  
Michael Edidin
Keyword(s):  
Cell Surface ◽  
Membrane Lipids ◽  
Surface Membrane ◽  
Lateral Diffusion ◽  
Cell Types ◽  
Membrane Domains ◽  
Membrane Biology ◽  
Morphological Polarity ◽  
Discrete Domains ◽  
Membrane Components

Cell surface membranes are based on a fluid lipid bilayer and models of the membranes' organization have emphasised the possibilities for lateral motion of membrane lipids and proteins within the bilayer. Two recent trends in cell and membrane biology make us consider ways in which membrane organization works against its inherent fluidity, localizing both lipids and proteins into discrete domains. There is evidence for such domains, even in cells without obvious morphological polarity and organization [Table 1]. Cells that are morphologically polarised, for example epithelial cells, raise the issue of membrane domains in an accute form.The technique of fluorescence photobleaching and recovery, FPR, was developed to measure lateral diffusion of membrane components. It has also proven to be a powerful tool for the analysis of constraints to lateral mobility. FPR resolves several sorts of membrane domains, all on the micrometer scale, in several different cell types.

scholarly journals The Glycine Lipids ofBacteroides thetaiotaomicronAre Important for Fitness during GrowthIn VivoandIn Vitro

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Alli Lynch ◽  
Seshu R. Tammireddy ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
David J. Clarke
Keyword(s):  
Amino Acid ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Cellular Membrane ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Acyltransferase Activity ◽  
Content Type ◽  
Health And Disease ◽  
And Function

ABSTRACTAcylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by theN-acylation of the amino acid, and this is followed by subsequentO-acylation of the acylated molecule, resulting in the production of the mature diacylated amino acid lipid. In this study, we use both genetics and liquid chromatography-mass spectrometry (LC-MS) to characterize the biosynthesis and function of a diacylated glycine lipid (GL) species produced inBacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, namedglsBin this study, that encodes anN-acyltransferase activity responsible for the production of a monoacylated glycine calledN-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of theBacteroidalesgenomes sequenced so far, theglsBgene is located immediately downstream from a gene, namedglsA, that is also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that the coexpression ofglsBandglsAresults in the production of GL inEscherichia coli. We constructed a deletion mutant of theglsBgene inB. thetaiotaomicron, and we confirm thatglsBis required for the production of GL inB. thetaiotaomicron. Moreover, we show thatglsBis important for the ability ofB. thetaiotaomicronto adapt to stress and colonize the mammalian gut. Therefore, this report describes the genetic requirements for the biosynthesis of GL, a diacylated amino acid species that contributes to fitness in the human gut bacteriumB. thetaiotaomicron.IMPORTANCEThe gut microbiome has an important role in both health and disease of the host. The mammalian gut microbiome is often dominated by bacteria from theBacteroidales, an order that includesBacteroidesandPrevotella. In this study, we have identified an acylated amino acid, called glycine lipid, produced byBacteroides thetaiotaomicron, a beneficial bacterium originally isolated from the human gut. In addition to identifying the genes required for the production of glycine lipids, we show that glycine lipids have an important role during the adaptation ofB. thetaiotaomicronto a number of environmental stresses, including exposure to either bile or air. We also show that glycine lipids are important for the normal colonization of the murine gut byB. thetaiotaomicron. This work identifies glycine lipids as an important fitness determinant inB. thetaiotaomicronand therefore increases our understanding of the molecular mechanisms underpinning colonization of the mammalian gut by beneficial bacteria.

scholarly journals Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

2020 ◽  
Author(s):  
Jesus A. Silvas ◽  
Alexander S. Jureka ◽  
Anthony M. Nicolini ◽  
Stacie A. Chvatal ◽  
Christopher F. Basler
Keyword(s):  
Lipid Metabolism ◽  
Fatty Acid Synthetase ◽  
Cellular Membrane ◽  
Fatty Acyl ◽  
Membrane Dynamics ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Virus Growth ◽  
Membrane Biology ◽  
Triacsin C

ABSTRACTTherapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity.

scholarly journals Dynamic proteomics of HSV1 infection reveals molecular events that govern non-stochastic infection outcomes

2016 ◽  
Author(s):  
Nir Drayman ◽  
Omer Karin ◽  
Avi Mayo ◽  
Tamar Danon ◽  
Lev Shapira ◽  
...  
Keyword(s):  
Single Cells ◽  
Infection Process ◽  
Human Pathogen ◽  
Herpes Simplex Virus 1 ◽  
Host Interactions ◽  
Protein Levels ◽  
Molecular Events ◽  
Proteomics Approach ◽  
Infected Cells ◽  
Simplex Virus

AbstractViral infection is usually studied at the level of cell populations, averaging over hundreds of thousands of individual cells. Moreover, measurements are typically done by analyzing a few time points along the infection process. While informative, such measurements are limited in addressing how cell variability affects infection outcome. Here we employ dynamic proteomics to study virus-host interactions, using the human pathogen Herpes Simplex virus 1 as a model. We tracked >50,000 individual cells as they respond to HSV1 infection, allowing us to model infection kinetics and link infection outcome (productive or not) with the cell state at the time of initial infection. We find that single cells differ in their preexisting susceptibility to HSV1, and that this is partially mediated by their cell-cycle position. We also identify specific changes in protein levels and localization in infected cells, attesting to the power of the dynamic proteomics approach for studying virus-host interactions.

scholarly journals Mucosal microbial parasites/symbionts in health and disease: an integrative overview

Parasitology ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. 1109-1115 ◽  
Author(s):  
Robert P. Hirt
Keyword(s):  
Host Interactions ◽  
Detection Techniques ◽  
Symbiotic Relationships ◽  
Life Styles ◽  
Mucosal Surfaces ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions ◽  
Species Being

AbstractMicrobial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host–parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites–microbiota–host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host–microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host–microbe interactions in both human health and disease.

scholarly journals Nutraceutical Boom in Cancer: Inside the Labyrinth of Reactive Oxygen Species

2020 ◽  
Vol 21 (6) ◽  
pp. 1936 ◽  
Author(s):  
Maura Calvani ◽  
Amada Pasha ◽  
Claudio Favre
Keyword(s):  
Well Being ◽  
Epidemiological Studies ◽  
Long Term Results ◽  
Negative Effects ◽  
Cell Growth Arrest ◽  
Host Interactions ◽  
Health And Disease ◽  
Pros And Cons ◽  
The Individual

In recent years, epidemiological studies have shown that food is a very powerful means for maintaining a state of well-being and for health prevention. Many degenerative, autoimmune and neoplastic diseases are related to nutrition and the nutrient–organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drugs response; therefore, these food–host interactions can influence the individual predisposition to disease and its potential therapeutic response. Do nutraceuticals have positive or negative effects during chemotherapy? The use of nutraceutical supplements in cancer patients is a controversial debate without a definitive conclusion to date. During cancer treatment, patients take nutraceuticals to alleviate drug toxicity and improve long-term results. Some nutraceuticals may potentiate the effect of cytotoxic chemotherapy by inducing cell growth arrest, cell differentiation, and alteration of the redox state of cells, but in some cases, high levels of them may interfere with the effectiveness of chemotherapy, making cancer cells less reactive to chemotherapy. In this review, we highlighted the emerging opinions and data on the pros and cons on the use of nutraceutical supplements during chemotherapy.

scholarly journals Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 294 ◽  
Author(s):  
Eveliina Taavitsainen ◽  
Maarit Kortesoja ◽  
Tanja Bruun ◽  
Niklas G. Johansson ◽  
Leena Hanski
Keyword(s):  
Chlamydia Pneumoniae ◽  
Concomitant Administration ◽  
Productive Infection ◽  
Intracellular Bacteria ◽  
Bacterial Eradication ◽  
Human Pathogen ◽  
Quantitative Culture ◽  
Phenotypic Switch ◽  
Host Interactions ◽  
Adjuvant Therapies

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia–host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.

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