Metabolic glycoengineering of Staphylococcus aureus reduces its adherence to human T24 bladder carcinoma cells

Memmel, Elisabeth; Homann, Arne; Oelschlaeger, Tobias A.; Seibel, Jürgen

doi:10.1039/c3cc43424a

Cited by 28 publications

(34 citation statements)

References 21 publications

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“…For the study of biomolecules, the advent of click chemistry has brought about powerful new tools to probe trafficking, metabolism, or formation of higher molecular complexes (15)(16)(17)(18)(19)(20). Click chemistry uses compounds containing terminal azido groups or alkynes allowing for bio-orthogonal reactions with suitable fluorophores.…”

mentioning

confidence: 99%

A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells

Collenburg

Walter

Burgert

et al. 2016

The Journal of Immunology

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Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools to further study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions to fluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells.

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confidence: 99%

A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells

Collenburg

Walter

Burgert

et al. 2016

The Journal of Immunology

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“…[402] Thecell surface of the Grampositive bacterium Staphylococcus aureus,could be visualized using MGE with N-azidoacetylglucosamine (GlcNAz). [403] After labeling with af luorescent dye,t he adherence of the labeled bacteria to cultured cells was reduced.…”

Section: Reviewsmentioning

confidence: 99%

Metabolic Glycoengineering with N‐Acyl Side Chain Modified Mannosamines

2016

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In metabolic glycoengineering (MGE), cells or animals are treated with unnatural derivatives of monosaccharides. After entering the cytosol, these sugar analogues are metabolized and subsequently expressed on newly synthesized glycoconjugates. The feasibility of MGE was first discovered for sialylated glycans, by using N-acyl-modified mannosamines as precursor molecules for unnatural sialic acids. Prerequisite is the promiscuity of the enzymes of the Roseman-Warren biosynthetic pathway. These enzymes were shown to tolerate specific modifications of the N-acyl side chain of mannosamine analogues, for example, elongation by one or more methylene groups (aliphatic modifications) or by insertion of reactive groups (bioorthogonal modifications). Unnatural sialic acids are incorporated into glycoconjugates of cells and organs. MGE has intriguing biological consequences for treated cells (aliphatic MGE) and offers the opportunity to visualize the topography and dynamics of sialylated glycans in vitro, ex vivo, and in vivo (bioorthogonal MGE).

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“…visualized LPS biosynthesis in live bacteria using azide-Kdo and Cu(I)-catalysed click chemistry with a fluorescent alkyne and a biocompatible copper-chelator; these authors demonstrated that only Gram-negative bacteria were visualized using this approach. 60 Additionally, GlcNAz-labelled glycans have been imaged on the surface of H. pylori 67 and S. aureus 68 cells. Each of these examples demonstrates the utility of MOE as a strategy to image bacterial glycans.…”

Section: Covalent Targeting Of Bacterial Glycans With Therapeuticsmentioning

confidence: 99%

Glycans in pathogenic bacteria – potential for targeted covalent therapeutics and imaging agents

2014

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A substantial obstacle to the existing treatment of bacterial diseases is the lack of specific probes that can be used to diagnose and treat pathogenic bacteria in a selective manner while leaving the microbiome largely intact. To tackle this problem, there is an urgent need to develop pathogen-specific therapeutics and diagnostics. Here, we describe recent evidence that indicates distinctive glycans found exclusively on pathogenic bacteria could form the basis of targeted therapeutic and diagnostic strategies. In particular, we highlight the use of metabolic oligosaccharide engineering to covalently deliver therapeutics and imaging agents to bacterial glycans.

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Metabolic glycoengineering of Staphylococcus aureus reduces its adherence to human T24 bladder carcinoma cells

Cited by 28 publications

References 21 publications

A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells

A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells

Metabolic Glycoengineering with N‐Acyl Side Chain Modified Mannosamines

Glycans in pathogenic bacteria – potential for targeted covalent therapeutics and imaging agents

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