Related Experiment Video
Updated: Jan 5, 2026

Introducing Shear Stress in the Study of Bacterial Adhesion
Published on: September 2, 2011
Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili
Zoe Virion1, Stéphane Doly2, Kusumika Saha2
1Inserm, U1151, CNRS UMR 8253, Institut-Necker-Enfants-Malades, Université de Paris, Paris, France.
Abstract:
Meningococcus utilizes β-arrestin selective activation of endothelial cell β2 adrenergic receptor (β2AR) to cause meningitis in humans. Molecular mechanisms of receptor activation by the pathogen and of its species selectivity remained elusive. We report that β2AR activation requires two asparagine-branched glycan chains with terminally exposed N-acetyl-neuraminic acid (sialic acid, Neu5Ac) residues located at a specific distance in its N-terminus, while being independent of surrounding amino-acid residues. Meningococcus triggers receptor signaling by exerting direct and hemodynamic-promoted traction forces on β2AR glycans. Similar activation is recapitulated with beads coated with Neu5Ac-binding lectins, submitted to mechanical stimulation. This previously unknown glycan-dependent mode of allosteric mechanical activation of a G protein-coupled receptor contributes to meningococcal species selectivity, since Neu5Ac is only abundant in humans due to the loss of CMAH, the enzyme converting Neu5Ac into N-glycolyl-neuraminic acid in other mammals. It represents an additional mechanism of evolutionary adaptation of a pathogen to its host.
Insights
Meningococcus bacteria activate human β2 adrenergic receptors (β2AR) through mechanical forces on its sugar chains, not amino acids. This glycan-dependent activation explains pathogen species selectivity in humans.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Neisseria meningitidis (meningococcus) causes meningitis by activating human endothelial cell β2 adrenergic receptors (β2AR).
- The precise molecular mechanisms of this pathogen-induced receptor activation and its species selectivity were previously unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms by which meningococcus activates β2AR.
- To understand the basis of meningococcal species selectivity in host infection.
Main Methods:
- Investigated the role of N-terminal glycan chains and mechanical forces in β2AR activation by meningococcus.
- Utilized beads coated with N-acetyl-neuraminic acid (Neu5Ac)-binding lectins to mimic pathogen-induced mechanical stimulation.
Main Results:
- β2AR activation by meningococcus depends on two specific N-terminal glycan chains with terminal N-acetyl-neuraminic acid (Neu5Ac) residues, independent of surrounding amino acids.
- Meningococcus triggers β2AR signaling via direct and hemodynamic-promoted traction forces on these glycans.
- Mechanical stimulation of Neu5Ac-coated beads recapitulated this activation mechanism.
Conclusions:
- Discovered a novel, glycan-dependent, allosteric mechanical mode of G protein-coupled receptor activation.
- This mechanism explains meningococcal species selectivity, as abundant human Neu5Ac contrasts with its lower levels in other mammals due to CMAH enzyme loss.
- Identified a new pathway for pathogen adaptation to its host environment.
Related Concept Videos
Fimbriae, Pili, and Axial Filaments
GPCRs Regulate Adenylyl Cylase Activity
Adherens Junctions
Adherens Junctions are Dynamic
Formation of Lipopolysaccharides
Sympathetic Signaling
Sympathetic preganglionic fibers release the neurotransmitter acetylcholine (ACh) onto the ganglionic neurons in the...
Tension Response at Adherens Junctions
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...

