Helicobacter pylori cholesteryl glucosides interfere with host membrane phase and affect type IV secretion system function during infection in AGS cells

Summary Helicobacter pylori infection is an aetiological cause of gastric disorders worldwide. H. pylori has been shown to assimilate and convert host cholesterol into cholesteryl glucosides (CGs) by cholesterol‐α‐glucosyltransferase encoded by capJ. Here, we show that CapJ‐deficient (ΔcapJ) H. pylo...

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Bibliographic Details
Published in:Molecular microbiology 2012-01, Vol.83 (1), p.67-84
Main Authors: Wang, Hung-Jung, Cheng, Wen-Chi, Cheng, Hsin-Hung, Lai, Chih-Ho, Wang, Wen-Ching
Format: Article
Language:English
Subjects:
Antigens, Bacterial - genetics
Antigens, Bacterial - metabolism
Bacterial infections
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacterial Secretion Systems
Bacteriology
Biological and medical sciences
Cell Line, Tumor
Cell Membrane - microbiology
Cholesterol - analogs & derivatives
Cholesterol - metabolism
Fundamental and applied biological sciences. Psychology
Genotype & phenotype
Glucose
Gram-negative bacteria
Helicobacter Infections - microbiology
Helicobacter pylori
Helicobacter pylori - genetics
Helicobacter pylori - metabolism
Humans
Microbiology
Miscellaneous
Mutation
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Summary:Summary Helicobacter pylori infection is an aetiological cause of gastric disorders worldwide. H. pylori has been shown to assimilate and convert host cholesterol into cholesteryl glucosides (CGs) by cholesterol‐α‐glucosyltransferase encoded by capJ. Here, we show that CapJ‐deficient (ΔcapJ) H. pylori resulted in greatly reduced type IV secretion system (TFSS)‐associated activities, including the hummingbird phenotype of AGS cells, IL‐8 production, CagA translocation/phosphorylation and CagA‐mediated signalling events. Complementation of the ΔcapJ mutation with wild type cagJ or by adding CGs‐containing lysates or exogenous fluorophore‐tagged CGs reversed the mutant phenotypes. We also show that the wild‐type but not ΔcapJ H. pylori recruited raft‐associated components to sites of bacterial attachment. Fluorescence recovery after photobleaching (FRAP) analysis of AGS cells treated with fluorescence‐tagged cholesterol/CGs revealed that there was a higher proportion of CGs associated with immobile fractions. CGs‐associated membranes were also more resistant to a cold detergent extraction. Thus, we propose that CGs synthesized by H. pylori around host‐pathogen contact sites partition in detergent‐resistant membranes (DRMs), alters lateral‐phase segregation in membrane and reorganizes membrane architecture. These processes together promote the formation of a functional TFSS and H. pylori infection.
ISSN:0950-382X
1365-2958
DOI:10.1111/j.1365-2958.2011.07910.x