A lipid zipper triggers bacterial invasion

Eierhoff, Thorsten; Bastian, Björn; Thuenauer, Roland; Madl, Josef; Audfray, Aymeric; Aigal, Sahaja; Juillot, Samuel; Rydell, Gustaf E.; Müller, Stefan K; Bentzmann, Sophie de; Imberty, Anne; Fleck, Christian; Römer, Winfried

doi:10.1073/pnas.1402637111

Cited by 126 publications

(178 citation statements)

References 53 publications

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“…We calculated membrane thickness as the distance between phosphorus atoms in the two monolayers (L m ) ( Table 3, column 5). L m does not change much for low Gb 3 concentrations, but for high S-Gb 3 concentrations, this value increases signicantly (a similar conclusion was made using Xray diffraction 16 ). We did not report any value for 100% Gb 3 since it is not a planar bilayer.…”

supporting

confidence: 72%

“…5. A similar l o phase is present in a phase-separated lipid bilayer composed of DOPC, sphingomyelin, cholesterol and porcine Gb 3 . Binding of STxB to the l o phase of this membrane does not induce tubular invagination.…”

Section: 12mentioning

confidence: 85%

“…Phase behaviour of such a bilayer is strongly inuenced by STxB clustering as well as the saturation levels and length of the Gb 3 fatty acyl chain. 11,13,15 Despite the important cellular roles of Gb 3 and its signicant impact on the physical behaviour of the lipid bilayers, it has not been studied by simulations before. Therefore, we use all-atom MD simulations to investigate a mixed bilayer of DOPC and Gb 3 with two different acyl chain compositions, Gb 3 -22 : 0 (Gb 3 with a saturated acyl chain with 22 carbon atoms) and Gb 3 -22 : 1 (Gb 3 with an unsaturated acyl chain with 22 carbon atoms and a trans-double bound in C 13 -C 14 ).…”

Section: 10-12mentioning

confidence: 99%

“…Force eld parameters for Gb 3 The Gb 3 lipid contains three sugar moieties, aGal(1-4), bGal (1)(2)(3)(4) and bGlc (Blue segment of Fig. 1A), which are connected to ceramide.…”

mentioning

confidence: 99%

“…36 The calculations were performed using the GAUSSIAN 09 program. 37 We considered 4 model compounds, (1) CH 2 ]CH-CH 2 -OH, (2) CH 3 -CH 2 -CH 2 -OH, (3) CH 3 -CH]CH-CH 3 and (4) CH 3 -CH]CH-CH 2 -OH. The inclusion of enumerated compounds into consideration was necessary to ensure reasonable transferability of the assigned charges.…”

mentioning

confidence: 99%

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The effects of globotriaosylceramide tail saturation level on bilayer phases

et al. 2015

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Globotriaosylceramide (Gb 3 ) is a glycosphingolipid present in the plasma membrane that is the natural receptor of the bacterial Shiga toxin. The unsaturation level of Gb 3 acyl chains has a drastic impact on lipid bilayer properties and phase behaviour, and on many Gb 3 -related cellular processes. For example:the Shiga toxin B subunit forms tubular invaginations in the presence of Gb 3 with an unsaturated acyl chain (U-Gb 3 ), while in the presence of Gb 3 with a saturated acyl chain (S-Gb 3 ) such invagination does not occur. We have used all-atom molecular dynamics simulations to investigate the effects of the Gb 3 concentration and its acyl chain saturation on the phase behaviour of a mixed bilayer of dioleoylphosphatidylcholine and Gb 3 . The simulation results show that: (1) the Gb 3 acyl chains (longer tails) from one leaflet interdigitate into the opposing leaflet and lead to significant bilayer rigidification and immobilisation of the lipid tails. S-Gb 3 can form a highly ordered, relatively immobile phase which is resistant to bending while these changes for U-Gb 3 are not significant. (2) At low concentrations of Gb 3 , U-Gb 3 and S-Gb 3 have a similar impact on the bilayer reminiscent of the effect of sphingomyelin lipids and (3) At higher Gb 3 concentrations, U-Gb 3 mixes better with dioleoylphosphatidylcholine than S-Gb 3 .Our simulations also provide the first molecular level structural model of Gb 3 in membranes.

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supporting

confidence: 72%

Section: 12mentioning

confidence: 85%

Section: 10-12mentioning

confidence: 99%

“…Force eld parameters for Gb 3 The Gb 3 lipid contains three sugar moieties, aGal(1-4), bGal (1)(2)(3)(4) and bGlc (Blue segment of Fig. 1A), which are connected to ceramide.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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The effects of globotriaosylceramide tail saturation level on bilayer phases

et al. 2015

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Animal Glycolipids

Schnaar

2015

Encyclopedia of Life Sciences

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Glycolipids are integral components of animal cell membranes, composed of a glycan covalently linked to a lipid. They include glycosphingolipids (GSLs) (ceramide‐linked), glycoglycerolipids (diacylglycerol‐ or alkylacylglycerol‐linked) and glycosylphosphatidylinositols (GPIs) (phosphatidylinositol‐linked). Their lipid components are embedded in a cell membrane with their glycans extending outwards where they interact with components in the plane of the same membrane or with glycan‐binding proteins, including soluble proteins and those on surfaces of other cells. Most animal glycolipids are GSLs, which can be as simple as ceramide monosaccharides or as large and complex as branched ceramide octadecasaccharides. Animal glycoglycerolipids are a simpler family, primarily galactose or sulphogalactose linked to glycerolipid. GPIs are glycans attached to the common membrane lipid phosphatidylinositol at one end and to a protein at the other, anchoring the protein to the membrane. Animal glycolipids serve diverse and essential functions in cell physiology in animals as simple as Caenorhabditis elegans and as complex as humans. Key Concepts Animal glycolipids are amphipathic molecules composed of a lipid embedded in a cell membrane and a glycan extending outwards. Most animal glycolipids are glycosphingolipids (GSLs), glycans carried on a ceramide lipid core. GSL glycans can be as simple as a single neutral sugar (glucosylceramide and galactosylceramide) or can be large, complex, branched and/or charged. GSLs are categorised as neutral GSLs, sulphated GSLs or gangliosides (sialic acid containing GSLs). Animal GSLs are named based on seven distinct neutral tetrasaccharide cores referred to as: ganglio‐, lacto‐, neolacto‐, globo‐, isoglobo‐, mollu‐ and arthro‐series. Animal glycoglycerolipids include galactose and 3‐sulphogalactose bound to diacylglycerol or alkylacylglycerol. They are scarce except in testes, where they are the major glycolipids and are required for spermatogenesis. Animal glycosylphosphatidylinositols (GPIs) consist of a core tetrasaccharide in glycosidic linkage to the inositol of phosphatidylinositol, a common membrane phospholipid. Animal GPIs carry a distal ethanolamine group, the terminal amine of which is linked via amide linkage to a select group of proteins, anchoring them to the membrane. Animal glycolipids tend to associate into functional microdomains in the plane of the membrane, often with sphingomyelin, cholesterol and select signalling proteins. GSLs function by binding laterally to molecules in the same membrane to regulate their activities (cis regulation) or by acting as receptors for soluble or cell surface glycan binding proteins (trans recognition).

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Bacteria‐Targeting Photodynamic Nanoassemblies for Efficient Treatment of Multidrug‐Resistant Biofilm Infected Keratitis

Zhu

Sun

et al. 2021

Adv Funct Materials

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Multidrug‐resistant Pseudomonas aeruginosa (MDR‐P. aeruginosa) cannot be extirpated with any of the antipseudomonal antibiotics available in clinic because P. aeruginosa exhibit natural resistance to antibiotics and form a stable biofilm. Biofilm formed by P. aeruginosa is a leading cause of bacterial keratitis which may cause corneal perforation and even blindness. Antibacterial photodynamic therapy (aPDT) is a promising bactericidal method in combatting drug‐resistant bacteria. Unfortunately, the use of broad‐spectrum aPDT that kills bacteria indiscriminately may lead to microbiota imbalance and cause serious side effects in normal cells. Herein, PαGal50‐b‐PGRB20, which can effectively disperse biofilms and selectively kill MDR‐P. aeruginosa inside biofilms by binding to Lec A in the extracellular polymeric substances and on the P. aeruginosa membrane with low phototoxicity caused by broad‐spectrum aPDT, is designed and synthesized. PαGal50‐b‐PGRB20 has bactericidal activities by damaging DNA, RNA, protein, and membrane. In vivo study of the MDR‐P. aeruginosa biofilm infected keratitis model demonstrates the potential of PαGal50‐b‐PGRB20 for a better corneal recovery. This work provides a dedicated antibacterial material for preferentially killing MDR‐P. aeruginosa over normal cells and other bacteria.

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A lipid zipper triggers bacterial invasion

Cited by 126 publications

References 53 publications

The effects of globotriaosylceramide tail saturation level on bilayer phases

The effects of globotriaosylceramide tail saturation level on bilayer phases

Animal Glycolipids

Bacteria‐Targeting Photodynamic Nanoassemblies for Efficient Treatment of Multidrug‐Resistant Biofilm Infected Keratitis

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