標題: Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence
作者: Jan, Hau-Ming
Chen, Yi-Chi
Shih, Yu-Yin
Huang, Yu-Chen
Tu, Zhijay
Ingle, Arun B.
Liu, Sheng-Wen
Wu, Ming-Shiang
Gervay-Hague, Jacquelyn
Mong, Kwok-Kong Tony
Chen, Yet-Ran
Lin, Chun-Hung
應用化學系
Department of Applied Chemistry
公開日期: 1-Jan-2016
摘要: 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 alpha-glucoside derivatives, including cholesteryl 6'-acyl and 6'-phosphatidyl alpha-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.
URI: http://dx.doi.org/10.1039/c6sc00889e
http://hdl.handle.net/11536/134156
ISSN: 2041-6520
DOI: 10.1039/c6sc00889e
期刊: CHEMICAL SCIENCE
Volume: 7
Issue: 9
起始頁: 6208
結束頁: 6216
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