Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution.

Abstract

Bacterial quorum-sensing autoinducers are small chemicals released to control microbial community behaviours. N-(3-oxo-dodecanoyl) homoserine lactone, the autoinducer of the Pseudomonas aeruginosa LasI-LasR circuitry, triggers significant cell death in lymphocytes. We found that this molecule is incorporated into the mammalian plasma membrane and induces dissolution of eukaryotic lipid domains. This event expels tumour necrosis factor receptor 1 into the disordered lipid phase for its spontaneous trimerization without its ligand and drives caspase 3-caspase 8-mediated apoptosis. In vivo, P. aeruginosa releases N-(3-oxo-dodecanoyl) homoserine lactone to suppress host immunity for its own better survival; conversely, blockage of caspases strongly reduces the severity of the infection. This work reveals an unknown communication method between microorganisms and the mammalian host and suggests interventions of bacterial infections by intercepting quorum-sensing signalling.

• Authors: Dingka Song, Junchen Meng, Jie Cheng, Zheng Fan, Pengyu Chen, Hefei Ruan, Zhongyuan Tu, Ning Kang, Nan Li, Ying Xu, Xiaobo Wang, Fei Shu, Libing Mu, Tengfei Li, Wenran Ren, Xin Lin, Jun Zhu, Xiaohong Fang, Matthias W Amrein, Weihui Wu, Li-Tang Yan, Junhong Lü, Tie Xia, Yan Shi
• Journal: Nature microbiology (Nat Microbiol) Vol. 4 Issue 1 Pg. 97-111 (01 2019) ISSN: 2058-5276 [Electronic] England
• PMID: 30510173 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Lipids
• N-(3-oxododecanoyl)homoserine lactone
• Receptors, Tumor Necrosis Factor, Type I
• Homoserine
• Caspase 3
• Caspase 8
• 4-Butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, metabolism)
• Animals
• Apoptosis (immunology)
• COS Cells
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Cell Line
• Chlorocebus aethiops
• HeLa Cells
• Homoserine (analogs & derivatives, metabolism)
• Humans
• Immune Evasion (immunology)
• Membrane Lipids (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pseudomonas Infections (immunology)
• Pseudomonas aeruginosa (immunology, pathogenicity)
• Quorum Sensing (immunology)
• RAW 264.7 Cells
• Receptors, Tumor Necrosis Factor, Type I (metabolism)