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

Hau Ming Jan, Yi Chi Chen, Yu Yin Shih, Yu Chen Huang, Zhijay Tu, Arun B. Ingle, Sheng Wen Liu, Ming Shiang Wu, Jacquelyn Gervay-Hague, Kwok Kong Tony Mong, Yet Ran Chen, Chun Hung Lin

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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.

Original languageEnglish (US)
Pages (from-to)6208-6216
Number of pages9
JournalChemical Science
Volume7
Issue number9
DOIs
StatePublished - 2016

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ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Jan, H. M., Chen, Y. C., Shih, Y. Y., Huang, Y. C., Tu, Z., Ingle, A. B., Liu, S. W., Wu, M. S., Gervay-Hague, J., Mong, K. K. T., Chen, Y. R., & Lin, C. H. (2016). Metabolic labelling of cholesteryl glucosides in: Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence. Chemical Science, 7(9), 6208-6216. https://doi.org/10.1039/c6sc00889e