Molecular Basis of Phosphatidyl-myo-inositol Mannoside Biosynthesis and Regulation in Mycobacteria*

Phosphatidyl-myo-inositol mannosides (PIMs) are unique glycolipids found in abundant quantities in the inner and outer membranes of the cell envelope of all Mycobacterium species. They are based on a phosphatidyl-myo-inositol lipid anchor carrying one to six mannose residues and up to four acyl chains. PIMs are considered not only essential structural components of the cell envelope but also the structural basis of the lipoglycans (lipomannan and lipoarabinomannan), all important molecules implicated in host-pathogen interactions in the course of tuberculosis and leprosy. Although the chemical structure of PIMs is now well established, knowledge of the enzymes and sequential events leading to their biosynthesis and regulation is still incomplete. Recent advances in the identification of key proteins involved in PIM biogenesis and the determination of the three-dimensional structures of the essential phosphatidyl-myo-inositol mannosyltransferase PimA and the lipoprotein LpqW have led to important insights into the molecular basis of this pathway.

• Publication year

  2010

• Venue

  Journal of Biological Chemistry

• Publication date

  2010-08-27

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.R110.168328PMID 20801880PMCID PMC2962455
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Diversity in Mycobacterium tuberculosis mannosylated cell wall determinants impacts adaptation to the host.

  2010cited by this paper
• Substrate-induced Conformational Changes in the Essential Peripheral Membrane-associated Mannosyltransferase PimA from Mycobacteria

  2009cited by this paper
• Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis.

  2009cited by this paper
• Essentials of glycobiology

  2009cited by this paper
• Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

  2009cited by this paper
• New Insights into the Early Steps of Phosphatidylinositol Mannoside Biosynthesis in Mycobacteria

  2009cited by this paper
• Mutations in pimE Restore Lipoarabinomannan Synthesis and Growth in a Mycobacterium smegmatis lpqW Mutant

  2008cited by this paper
• Analysis of a New Mannosyltransferase Required for the Synthesis of Phosphatidylinositol Mannosides and Lipoarbinomannan Reveals Two Lipomannan Pools in Corynebacterineae*

  2008cited by this paper
• Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli

  2008cited by this paper
• Glycosyltransferases: structures, functions, and mechanisms.

  2008cited by this paper
• Solution structure of Alg13: the sugar donor subunit of a yeast N-acetylglucosamine transferase.

  2008cited by this paper
• The immunomodulatory lipoglycans, lipoarabinomannan and lipomannan, are exposed at the mycobacterial cell surface.

  2008cited by this paper
• The mycobacterial cell envelope.

  2008cited by this paper
• High cationic charge and bilayer interface-binding helices in a regulatory lipid glycosyltransferase.

  2007cited by this paper
• Molecular Recognition and Interfacial Catalysis by the Essential Phosphatidylinositol Mannosyltransferase PimA from Mycobacteria*

  2007cited by this paper
• The glycosyltransferases of Mycobacterium tuberculosis - roles in the synthesis of arabinogalactan, lipoarabinomannan, and other glycoconjugates.

  2007cited by this paper
• Fine Discrimination in the Recognition of Individual Species of Phosphatidyl-myo-Inositol Mannosides from Mycobacterium tuberculosis by C-Type Lectin Pattern Recognition Receptors1

  2006cited by this paper
• PimE Is a Polyprenol-phosphate-mannose-dependent Mannosyltransferase That Transfers the Fifth Mannose of Phosphatidylinositol Mannoside in Mycobacteria*

  2006cited by this paper
• Identification of a Novel Protein with a Role in Lipoarabinomannan Biosynthesis in Mycobacteria*

  2006cited by this paper
• Hijacking of a substrate-binding protein scaffold for use in mycobacterial cell wall biosynthesis.

  2006cited by this paper
• Receptor-Mediated Recognition of Mycobacterium tuberculosis by Host Cells

  2005cited by this paper
• Function of Phosphatidylinositol in Mycobacteria*

  2005cited by this paper
• Tuberculosis and the tubercle bacillus.

  2005cited by this paper
• Compartmentalization of Lipid Biosynthesis in Mycobacteria*

  2005cited by this paper
• Biosynthesis of mycobacterial phosphatidylinositol mannosides.

  2004cited by this paper
• Biogenesis of the gram-negative bacterial outer membrane.

  2004cited by this paper
• Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response

  2004cited by this paper
• Biogenesis of the Gram-negative bacterial outer membrane.

  2004cited by this paper
• Thermodynamics of lipid-peptide interactions.

  2004cited by this paper
• Mannose metabolism is required for mycobacterial growth.

  2003cited by this paper
• Identification of the Required Acyltransferase Step in the Biosynthesis of the Phosphatidylinositol Mannosides of Mycobacterium Species*

  2003cited by this paper
• Acylation State of the Phosphatidylinositol Hexamannosides from Mycobacterium bovis Bacillus Calmette Guérin and Mycobacterium tuberculosis H37Rv and Its Implication in Toll-like Receptor Response*

  2003cited by this paper
• Characterization of a putative alpha-mannosyltransferase involved in phosphatidylinositol trimannoside biosynthesis in Mycobacterium tuberculosis.

  2002cited by this paper
• Lipopolysaccharide endotoxins.

  2002cited by this paper
• Definition of the First Mannosylation Step in Phosphatidylinositol Mannoside Synthesis

  2002cited by this paper
• Intrinsic lipid preferences and kinetic mechanism of Escherichia coli MurG.

  2002cited by this paper
• Acylation State of the Phosphatidylinositol Mannosides from Mycobacterium bovis Bacillus Calmette Guérin and Ability to Induce Granuloma and Recruit Natural Killer T Cells*

  2001cited by this paper
• Membrane binding and pore formation of the antibacterial peptide PGLa: thermodynamic and mechanistic aspects.

  2000cited by this paper
• Biosynthesis of Mycobacterial Lipoarabinomannan*

  1997cited by this paper
• The Phosphatidyl-myo-inositol Anchor of the Lipoarabinomannans from Mycobacterium bovis Bacillus Calmette Guérin

  1997cited by this paper
• A Mycobacterium smegmatis mutant with a defective inositol monophosphate phosphatase gene homolog has altered cell envelope permeability

  1997cited by this paper
• Identification of the surface-exposed lipids on the cell envelopes of Mycobacterium tuberculosis and other mycobacterial species

  1996cited by this paper
• Structural definition of acylated phosphatidylinositol mannosides from Mycobacterium tuberculosis: definition of a common anchor for lipomannan and lipoarabinomannan.

  1995cited by this paper
• Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria

  1993cited by this paper
• Lipoarabinomannan. Multiglycosylated form of the mycobacterial mannosylphosphatidylinositols.

  1992cited by this paper
• Evidence for the presence of a phosphatidylinositol anchor on the lipoarabinomannan and lipomannan of Mycobacterium tuberculosis.

  1990cited by this paper
• Subcellular distribution of mannophosphoinositides inMycobacterium smegmatis during growth

  1983cited by this paper
• Effect of growth temperature on the lipid composition of Mycobacterium smegmatis ATCC 607.

  1979cited by this paper
• Environmental effects on lipids of Mycobacterium phlei ATCC 354

  1977cited by this paper
• Biosynthesis of mannophosphoinositides by Mycobacterium phlei. The family of dimannophosphoinositides.

  1967cited by this paper
• Biosynthesis of mannophospholipids by Mycobacterium phlei.

  1966cited by this paper
• Complete structures of the glycophospholipids of mycobacteria.

  1965cited by this paper
• STRUCTURAL STUDIES ON THE MYO-INOSITOL MANNODIDES FROM THE GLYCOLIPIDS OF MYCOBACTERIUM TUBERCULOSIS AND MYCOBACTERIUM PHLEI.

  1964cited by this paper
• Structural studies on the myo-inositol phospholipids of Mycobacterium tuberculosis (var. bovis, strain BCG).

  1963cited by this paper
• THE CHEMISTRY OF THE LIPOIDS OF TUBERCLE BACILLI. XXI. THE POLYSACCHARIDE OCCURRING IN THE PHOSPHATIDE FROM THE HUMAN TUBERCLE BACILLI1

  1930cited by this paper
• THE CHEMISTRY OF THE LIPOIDS OF TUBERCLE BACILLI. XIV. THE OCCURRENCE OF INOSITE IN THE PHOSPHATIDE FROM HUMAN TUBERCLE BACILLI1

  1930cited by this paper

• Contribution of Proteins to Membrane and Cell Wall Structures in Mycobacterium tuberculosis.

  2026cites this paper
• Phospholipid Diversity and Biosynthesis Pathway in Bacteria: Potential Antibacterial Targets.

  2026cites this paper
• A molecular dynamics study of PIM2 lipid bilayer membranes.

  2026cites this paper
• Reviewing Glycosyl‐Inositols: Natural Occurrence, Biological Roles, and Synthetic Techniques

  2025cites this paper
• Co-administration of a synthetic saccharide conjugate vaccine with BCG provides synergistic protection against murine tuberculosis.

  2025cites this paper
• Label-free electrochemical-based biosensor for gene-phosphatidylinositol mannosides detection in urine for the determination of multidrug-resistant tuberculosis

  2025cites this paper
• A glycosylated lipooctapeptide promotes uptake and growth of Mycobacterium abscessus in the host

  2025cites this paper
• Mechanistic studies of mycobacterial glycolipid biosynthesis by the mannosyltransferase PimE

  2025cites this paper
• The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth

  2024cites this paper
• Metabolic phenotyping and global functional analysis facilitate metabolic signature discovery for tuberculosis treatment monitoring.

  2024cites this paper
• The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth

  2023cites this paper
• New therapeutic strategies for Mycobacterium abscessus pulmonary diseases – untapping the mycolic acid pathway

  2023cites this paper
• Drug-Tolerant Mycobacterium tuberculosis Adopt Different Survival Strategies in Alveolar Macrophages of Patients with Pulmonary Tuberculosis

  2023cites this paper
• Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection

  2023cites this paper
• Azido Inositol Probes Enable Metabolic Labeling of Inositol-Containing Glycans and Reveal an Inositol Importer in Mycobacteria.

  2023cites this paper
• Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane

  2023cites this paper
• Deciphering the mannose transfer mechanism of mycobacterial PimE by molecular dynamics simulations.

  2023cites this paper
• An update on Mycobacterium tuberculosis lipoproteins.

  2023cites this paper
• Identification of Microorganisms Dwelling on the 19th Century Lanna Mural Paintings from Northern Thailand Using Culture-Dependent and -Independent Approaches

  2022cites this paper
• Inhibition of the Niemann-Pick C1 protein is a conserved feature of multiple strains of pathogenic mycobacteria

  2022cites this paper
• Understanding the Mannose Transfer Mechanism of Mycobacterial Phosphatidyl-myo-inositol Mannosyltransferase A from Molecular Dynamics Simulations

  2022cites this paper
• Structure of mycobacterial respiratory complex I

  2022cites this paper
• Bacterial glycosylation, it’s complicated

  2022cites this paper
• In-silico identification of critical residues in the mannose-transfer mechanism of phosphatidyl-myo-inositol mannosyltransferase B'.

  2022cites this paper
• A Review on Lipid Bilayer for Bio Molecular Caging

  2021cites this paper
• Molecular ruler mechanism and interfacial catalysis of the integral membrane acyltransferase PatA

  2021cites this paper
• The Phosphatidyl-myo-Inositol Dimannoside Acyltransferase PatA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo

  2021cites this paper
• Tanshinones from Salvia miltiorrhiza inhibit Mycobacterium tuberculosis via disruption of the cell envelope surface and oxidative stress.

  2021cites this paper
• Functional analysis and enzyme characterization of Mannose-1-phosphate guanylyl transferase (ManB) from Mycobacterium tuberculosis.

  2021cites this paper
• Application of antigenic biomarkers for Mycobacterium tuberculosis

  2020cites this paper
• Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell Envelope.

  2020cites this paper
• Host Cell Targets of Released Lipid and Secreted Protein Effectors of Mycobacterium tuberculosis

  2020cites this paper
• The Two-Component Locus MSMEG_0244/0246 Together With MSMEG_0243 Affects Biofilm Assembly in M. smegmatis Correlating With Changes in Phosphatidylinositol Mannosides Acylation

  2020cites this paper
• Dissecting the Structural and Chemical Determinants of the "Open-to-Closed" Motion in the Mannosyltransferase PimA from Mycobacteria.

  2020cites this paper
• Preparation and Application of 13C-Labeled myo-Inositol to Identify New Catabolic Products in Inositol Metabolism in Lactobacillus casei.

  2020cites this paper
• Unveiling the activation dynamics of a fold-switch bacterial glycosyltransferase by 19F NMR

  2020cites this paper
• The key entity of a DCAR agonist, phosphatidylinositol mannoside Ac1PIM1: its synthesis and immunomodulatory function.

  2020cites this paper
• Recognition of Mycobacteria by Dendritic Cell Immunoactivating Receptor.

  2020cites this paper
• Lipids of Clinically Significant Mycobacteria

  2020cites this paper
• Techniques to Understand Mycobacterial Lipids and Use of Lipid-Based Nanoformulations for Tuberculosis Management

  2020cites this paper
• Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR

  2020cites this paper
• The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis.

  2019cites this paper
• Mycobacteria and their sweet proteins: An overview of protein glycosylation and lipoglycosylation in M. tuberculosis.

  2019cites this paper
• MpbR, an essential transcriptional factor for Mycobacterium tuberculosis survival in the host, modulates PIM biosynthesis and reduces innate immune responses.

  2019cites this paper
• Synthetic Lipomannan Glycan Microarray Reveals the Importance of α(1,2) Mannose Branching in DC-SIGN Binding.

  2019cites this paper
• Underestimated Manipulative Roles of Mycobacterium tuberculosis Cell Envelope Glycolipids During Infection

  2019cites this paper
• In Vivo Methods to Study Protein–Protein Interactions as Key Players in Mycobacterium Tuberculosis Virulence

  2019cites this paper
• 1 In Vivo Methods to Study Protein-Protein Interactions 2 as Key Players in Mycobacterium tuberculosis 3 Virulence 4

  2019cites this paper
• Structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase reveals mechanism of substrate binding and metal catalysis

  2019cites this paper
• All-atom Molecular Dynamics model for mycobacterial plasma membrane

  2019cites this paper
• Over-expression of Tgs1 in Mycobacterium marinum enhances virulence in adult zebrafish.

  2019cites this paper
• The mycobacterial cell envelope — a moving target

  2019cites this paper
• Cloning and Partial Characterization of an Endo-α-(1→6)-d-Mannanase Gene from Bacillus circulans

  2019cites this paper
• University of Groningen 3-Hydroxybenzoate 6-Hydroxylase from Rhodococcus jostii RHA 1 Contains a Phosphatidylinositol Cofactor

  2018cites this paper
• Cell envelope lipids in the pathophysiology of Mycobacterium tuberculosis.

  2018cites this paper
• Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes

  2018cites this paper
• Streptomyces coelicolor strains lacking polyprenol phosphate mannose synthase and protein O-mannosyl transferase are hyper-susceptible to multiple antibiotics

  2018cites this paper
• A five-component one-pot synthesis of phosphatidylinositol pentamannoside (PIM5)

  2017cites this paper
• Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth

  2017cites this paper
• Mycobacterium avium subsp. paratuberculosis (Map) Fatty Acids Profile Is Strain-Dependent and Changes Upon Host Macrophages Infection

  2017influential citation
• Imidazoles Induce Reactive Oxygen Species in Mycobacterium tuberculosis Which Is Not Associated with Cell Death

  2017cites this paper
• The Molecular Mechanism of Substrate Recognition and Catalysis of the Membrane Acyltransferase PatA from Mycobacteria.

  2017cites this paper
• Base-modified GDP-mannose derivatives and their substrate activity towards a yeast mannosyltransferase.

  2017cites this paper
• Knowns and unknowns of membrane lipid synthesis in streptomycetes.

  2017cites this paper
• 3-Hydroxybenzoate 6-Hydroxylase from Rhodococcus jostii RHA1 Contains a Phosphatidylinositol Cofactor

  2017cites this paper
• Comparative lipidomics of drug sensitive and resistant Mycobacterium tuberculosis reveals altered lipid imprints

  2017cites this paper
• Intracellular Membrane Organization in Mycobacteria

  2017cites this paper
• Innate signaling by mycolate esters of the cell wall of Mycobacterium tuberculosis and relevance for the development of adjuvants for subunit vaccines

  2017cites this paper
• Structural basis of phosphatidyl-myo-inositol mannosides biosynthesis in mycobacteria.

  2017cites this paper
• Biocompatibility of liposomes derived from microbial cells: an assesment towards Nanomedicine applications

  2016cites this paper
• Molecular Basis of Membrane Association by the Phosphatidylinositol Mannosyltransferase PimA Enzyme from Mycobacteria*

  2016cites this paper
• Lipoarabinomannan, and its related glycolipids, induce divergent and opposing immune responses to Mycobacterium tuberculosis depending on structural diversity and experimental variations.

  2016influential citation
• The conformational plasticity of glycosyltransferases.

  2016cites this paper
• Structural characterization of suppressor lipids by high-resolution mass spectrometry.

  2016cites this paper
• Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA

  2016cites this paper
• Bacterial membrane lipids: diversity in structures and pathways.

  2016cites this paper
• C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection.

  2016cites this paper
• Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity

  2015cites this paper
• High quality draft genome sequence of Corynebacterium ulceribovis type strain IMMIB-L1395T (DSM 45146T)

  2015cites this paper
• Pathophysiological Implications of Cell Envelope Structure in Mycobacterium tuberculosis and Related Taxa

  2015cites this paper
• High quality draft genome sequence of Corynebacterium ulceribovis type strain

  2015cites this paper
• Secondary structure reshuffling modulates glycosyltransferase function at the membrane.

  2015cites this paper
• Defining the Interaction of Human Soluble Lectin ZG16p and Mycobacterial Phosphatidylinositol Mannosides

  2015cites this paper
• Inositol-phosphodihydroceramides in the periodontal pathogen Tannerella forsythia: Structural analysis and incorporation of exogenous myo-inositol

  2015cites this paper
• The mycobacterial cell envelope-lipids.

  2014cites this paper
• Molecular and biochemical characterisation of mycobacterial cell wall drug targets - Lipoarabinomannan

  2014influential citation
• GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS FOR PROTEINS AND PHOSPHATIDYLINOSITOL MANNOSIDES STRUCTURE , OCCURRENCE , BIOCHEMISTRY AND FUNCTION 1 . Structure and Occurrence

  2014cites this paper
• Purification and characterization of the acyltransferase involved in biosynthesis of the major mycobacterial cell envelope glycolipid--monoacylated phosphatidylinositol dimannoside.

  2014cites this paper
• Structure-function relationships of membrane-associated GT-B glycosyltransferases.

  2014cites this paper
• The Phosphatidyl-myo-Inositol Mannosyltransferase PimA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo

  2014cites this paper
• Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

  2014cites this paper
• Mycobacterium tuberculosis Lipoprotein LprG Binds Lipoarabinomannan and Determines Its Cell Envelope Localization to Control Phagolysosomal Fusion

  2014cites this paper
• The cell envelope glycoconjugates of Mycobacterium tuberculosis

  2014cites this paper
• Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids.

  2014cites this paper
• Crystal structure and functional implications of LprF from Mycobacterium tuberculosis and M. bovis.

  2014cites this paper
• Genetics of Mycobacterial Arabinogalactan and Lipoarabinomannan Assembly

  2014cites this paper
• Metabolism of Plasma Membrane Lipids in Mycobacteria and Corynebacteria

  2013cites this paper
• Conformational Plasticity of the Essential Membrane-associated Mannosyltransferase PimA from Mycobacteria*

  2013cites this paper
• Synthesis, structural elucidation, and biochemical analysis of immunoactive glucuronosyl diacylglycerides of mycobacteria and corynebacteria.

  2013cites this paper
• Critical Roles for Lipomannan and Lipoarabinomannan in Cell Wall Integrity of Mycobacteria and Pathogenesis of Tuberculosis

  2013cites this paper