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Issue 9, 2016
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Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence

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Abstract

Helicobacter pylori infects approximately half of the human population and is the main cause of various gastric diseases. This pathogen is auxotrophic for cholesterol, which it converts upon uptake to various cholesteryl α-glucoside derivatives, including cholesteryl 6′-acyl and 6′-phosphatidyl α-glucosides (CAGs and CPGs). Owing to a lack of sensitive analytical methods, it is not known if CAGs and CPGs play distinct physiological roles or how the acyl chain component affects function. Herein we established a metabolite-labelling method for characterising these derivatives qualitatively and quantitatively with a femtomolar detection limit. The development generated an MS/MS database of CGds, allowing for profiling of all the cholesterol-derived metabolites. The subsequent analysis led to the unprecedented information that these bacteria acquire phospholipids from the membrane of epithelial cells for CAG biosynthesis. The resulting increase in longer or/and unsaturated CAG acyl chains helps to promote lipid raft formation and thus delivery of the virulence factor CagA into the host cell, supporting the idea that the host/pathogen interplay enhances bacterial virulence. These findings demonstrate an important connection between the chain length of CAGs and the bacterial pathogenicity.

Graphical abstract: Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence

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Publication details

The article was received on 25 Feb 2016, accepted on 28 May 2016 and first published on 03 Jun 2016


Article type: Edge Article
DOI: 10.1039/C6SC00889E
Citation: Chem. Sci., 2016,7, 6208-6216
  • Open access: Creative Commons BY license
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    Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence

    H. Jan, Y. Chen, Y. Shih, Y. Huang, Z. Tu, A. B. Ingle, S. Liu, M. Wu, J. Gervay-Hague, K. T. Mong, Y. Chen and C. Lin, Chem. Sci., 2016, 7, 6208
    DOI: 10.1039/C6SC00889E

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