scholarly journals Synthesis of a Di-Mycoloyl Tri-Arabinofuranosyl Glycerol Fragment of the Mycobacterial Cell Wall, Based on Synthetic Mycolic Acids

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3596
Author(s):  
Ali ◽  
Mohammed ◽  
Dulayymi ◽  
Baird
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Stereoselective Synthesis ◽  
Complex Mixtures ◽  
Mycolic Acids ◽  
Mycobacterial Cell ◽  
Antigenic Properties ◽  
Mycobacterial Cell Wall ◽  
Structural Classes

Fragments of mycobacterial cell walls such as arabinoglycerol mycolate and dimycoloyl diarabinoglycerol, comprising complex mixtures of mycolic acids, have immunostimulatory and antigenic properties. A related di-mycoloyl tri-arabinofuranosyl glycerol fragment has been isolated from cell wall hydrolysates. An effective stereoselective synthesis of tri-arabinofuranosyl glycerol, followed by coupling with stereochemically defined mycolic acids of different structural classes, to provide unique di-mycoloyl tri-arabinofuranosyl glycerols is now described.

scholarly journals MmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine

2019 ◽  
Vol 116 (23) ◽  
pp. 11241-11246 ◽  
Author(s):  
Chih-Chia Su ◽  
Philip A. Klenotic ◽  
Jani Reddy Bolla ◽  
Georgiana E. Purdy ◽  
Carol V. Robinson ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Envelope ◽  
Native Mass Spectrometry ◽  
Mycolic Acids ◽  
Mycobacterial Cell ◽  
Exact Function ◽  
Species Specific ◽  
Mycobacterial Cell Wall ◽  
Trehalose Monomycolate ◽  
Lipid Transporter

The cell envelope ofMycobacterium tuberculosisis notable for the abundance of mycolic acids (MAs), essential to mycobacterial viability, and of other species-specific lipids. The mycobacterial cell envelope is extremely hydrophobic, which contributes to virulence and antibiotic resistance. However, exactly how fatty acids and lipidic elements are transported across the cell envelope for cell-wall biosynthesis is unclear. Mycobacterial membrane protein Large 3 (MmpL3) is essential and required for transport of trehalose monomycolates (TMMs), precursors of MA-containing trehalose dimycolates (TDM) and mycolyl arabinogalactan peptidoglycan, but the exact function of MmpL3 remains elusive. Here, we report a crystal structure ofMycobacterium smegmatisMmpL3 at a resolution of 2.59 Å, revealing a monomeric molecule that is structurally distinct from all known bacterial membrane proteins. A previously unknown MmpL3 ligand, phosphatidylethanolamine (PE), was discovered inside this transporter. We also show, via native mass spectrometry, that MmpL3 specifically binds both TMM and PE, but not TDM, in the micromolar range. These observations provide insight into the function of MmpL3 and suggest a possible role for this protein in shuttling a variety of lipids to strengthen the mycobacterial cell wall.

scholarly journals Synthesis and Biological Aspects of Mycolic Acids: An Important Target AgainstMycobacterium tuberculosis

2008 ◽  
Vol 8 ◽  
pp. 720-751 ◽  
Author(s):  
Marcus Vinícius Nora de Souza ◽  
Marcelle de Lima Ferreira ◽  
Alessandra Campbell Pinheiro ◽  
Maurício Frota Saraiva ◽  
Mauro Vieira de Almeida ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Cell Walls ◽  
Important Class ◽  
Cellular Targets ◽  
Mycolic Acids ◽  
Important Target ◽  
Novel Drugs ◽  
Biological Aspects ◽  
Mycobacterial Cell Wall

Mycolic acids are an important class of compounds, basically found in the cell walls of a group of bacteria known as mycolata taxon, exemplified by the most famous bacteria of this group, theMycobacterium tuberculosis(M. tb.), the agent responsible for the disease known as tuberculosis (TB). Mycolic acids are important for the survival of M. tb. For example, they are able to help fight against hydrophobic drugs and dehydration, and also allow this bacterium to be more effective in the host's immune system by growing inside macrophages. Due to the importance of the mycolic acids for maintenance of the integrity of the mycobacterial cell wall, these compounds become attractive cellular targets for the development of novel drugs against TB. In this context, the aim of this article is to highlight the importance of mycolic acids in drug discovery.

Stereoselective synthesis of β-arabino glycosyl sulfones as potential inhibitors of mycobacterial cell wall biosynthesis

2009 ◽  
Vol 344 (6) ◽  
pp. 739-746 ◽  
Author(s):  
Benjamin Ayers ◽  
Hilary Long ◽  
Edith Sim ◽  
Iain A. Smellie ◽  
Brendan L. Wilkinson ◽  
...  
Keyword(s):  
Cell Wall ◽  
Stereoselective Synthesis ◽  
Cell Wall Biosynthesis ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall ◽  
Potential Inhibitors

scholarly journals Mycobacteriophage Ms6 LysB specifically targets the outer membrane of Mycobacterium smegmatis

Microbiology ◽  
2010 ◽  
Vol 156 (5) ◽  
pp. 1497-1504 ◽  
Author(s):  
Filipa Gil ◽  
Anna E. Grzegorzewicz ◽  
Maria João Catalão ◽  
João Vital ◽  
Michael R. McNeil ◽  
...  
Keyword(s):  
Cell Wall ◽  
Outer Membrane ◽  
Mycobacterium Smegmatis ◽  
Mycolic Acid ◽  
Head Group ◽  
Lipolytic Enzyme ◽  
Ester Bond ◽  
Mycolic Acids ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall

LysB, a mycobacteriophage Ms6-encoded protein, was previously identified as a lipolytic enzyme able to hydrolyse the ester bond in lipase and esterase substrates. In the present work, we show that LysB can hydrolyse lipids containing mycolic acids from the outer membrane of the mycobacterial cell wall. LysB was shown to hydrolyse the mycolic acids from the mycolyl-arabinogalactan–peptidoglycan complex where the mycolates of the inner leaflet of the outer membrane are covalently attached to an arabinosyl head group. In addition, treatment of the extractable lipids from Mycobacterium smegmatis, Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Ra with LysB showed that trehalose 6,6′-dimycolate (TDM), a trehalose diester of two mycolic acid molecules, was hydrolysed by the enzyme. We have also determined the structures of the mycolic acid molecules that form the M. smegmatis TDM. The identification of a phage-encoded enzyme that targets the outer membrane of the mycobacterial cell wall enhances our understanding of the mechanism of mycobacteriophage lysis.

scholarly journals MmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine

2019 ◽  
Author(s):  
Chih-Chia Su ◽  
Philip Klenotic ◽  
Jani Reddy Bolla ◽  
Georgiana Purdy ◽  
Carol Robinson ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Envelope ◽  
Native Mass Spectrometry ◽  
Mycolic Acids ◽  
Mycobacterial Cell ◽  
Exact Function ◽  
Species Specific ◽  
Mycobacterial Cell Wall ◽  
Trehalose Monomycolate ◽  
Lipid Transporter

The cell envelope of Mycobacterium tuberculosis is notable for the abundance of mycolic acids (MAs), which are essential to mycobacterial viability, and other species-specific lipids. The mycobacterial cell envelope is extremely hydrophobic, contributes to virulence and antibiotic resistance. Yet, exactly how fatty acids and lipidic elements are transported across the cell envelope for cell wall biosynthesis is unclear. Mycobacterial membrane protein Large 3 (MmpL3) is essential and required for transport of trehalose monomycolates (TMMs), precursors of MA containing trehalose dimycolates (TDM) and mycolyl arabinogalactan peptidoglycan (mAGP), but the exact function of MmpL3 remains elusive. Here, we report a high-resolution crystal structure of M. smegmatis MmpL3, revealing a monomeric molecule that is structurally distinct from all known bacterial membrane proteins. A previously unknown MmpL3 ligand, phosphatidylethanolamine (PE), was discovered inside this transporter. We also show, via native mass spectrometry, that MmpL3 specifically binds both TMM and PE, but not TDM, in the micromolar range. These observations provide insight into the function of MmpL3 and suggest a possible role for this protein in shuttling a variety of lipids to strengthen the mycobacterial cell wall.

Conserved Molecular Superlattices in a Series of Homologous Synthetic Mycobacterial Cell-Wall Lipids Forming Interdigitated Bilayers

Langmuir ◽  
2016 ◽  
Vol 32 (48) ◽  
pp. 12693-12701 ◽  
Author(s):  
Birte Martin-Bertelsen ◽  
Anan Yaghmur ◽  
Henrik Franzyk ◽  
Sarah Justesen ◽  
Jacob J. K. Kirkensgaard ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterial Cell ◽  
Mycobacterial Cell Wall
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