Pore formation by the Bordetella adenylate cyclase toxin in lipid bilayer membranes: Role of voltage and pH

The Gram-negative bacterium Bordetella pertussis is the cause of whooping cough. One of its pathogenicity factors is the adenylate cyclase toxin (CyaA) secreted by a Type I export system. The 1706 amino acid long CyaA (177 kDa) belongs to the continuously increasing family of repeat in toxin (RTX) toxins because it contains in its C-terminal half a high number of nine-residue tandem repeats. The protein exhibits cytotoxic and hemolytic activities that target primarily myeloid phagocytic cells expressing the αMβ2 integrin receptor (CD11b/CD18). CyaA represents an exception among RTX cytolysins because the first 400 amino acids from its N-terminal end possess a calmodulin-activated adenylate cyclase (AC) activity. The entry of the AC into target cells is not dependent on the receptor-mediated endocytosis pathway and penetrates directly across the cytoplasmic membrane of a variety of epithelial and immune effector cells. The hemolytic activity of CyaA is rather low, which may have to do with its rather low induced permeability change of target cells and its low conductance in lipid bilayer membranes. CyaA forms highly cation-selective channels in lipid bilayers that show a strong dependence on aqueous pH. The pore-forming activity of CyaA but not its single channel conductance is highly dependent on Ca2+ concentration with a half saturation constant of about 2 to 4 mM.

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Pores formed in lipid bilayer membranes by nystatin, Differences in its one-sided and two-sided action.

The Journal of General Physiology ◽

10.1085/jgp.65.4.515 ◽

1975 ◽

Vol 65 (4) ◽

pp. 515-526 ◽

Cited By ~ 147

Author(s):

A Marty ◽

A Finkelstein

Keyword(s):

Hydrogen Bonding ◽

Lipid Bilayer ◽

Pore Formation ◽

Plasma Membranes ◽

Bilayer Membrane ◽

Bilayer Structure ◽

Lipid Bilayer Membranes ◽

Bilayer Membranes ◽

The One

Nystatin and amphotericin B induce a cation-selective conductance when added to one side of a lipid bilayer membrane and an anion-selective conductance when added to both sides. The concentrations of antibiotic required for the one-sided action are comparable to those employed on plasma membranes and are considerably larger than those required for the two-sided action. We propose that the two-sided effect results from the formation of aqueous pores formed by the hydrogen bonding in the middle of the bilayer of two "half pores," whereas the one-sided effect results from the half pores alone. We discuss, in terms of the flexibility of bilayer structure and its thickness, how it is possible to have conducting half pores and "complete pores" in the same membrane. The role of sterol (cholesterol and ergosterol) in pore formation is also examined.

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Diffusion of complex objects embedded in free and supported lipid bilayer membranes: role of shape anisotropy and leaflet structure

Soft Matter ◽

10.1039/c3sm00073g ◽

2013 ◽

Vol 9 (19) ◽

pp. 4767 ◽

Cited By ~ 38

Author(s):

Brian A. Camley ◽

Frank L. H. Brown

Keyword(s):

Lipid Bilayer ◽

Shape Anisotropy ◽

Lipid Bilayer Membranes ◽

Complex Objects ◽

Supported Lipid Bilayer ◽

Bilayer Membranes

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[56] Use of lipid bilayer membranes to detect pore formation by toxins

Methods in Enzymology - Bacterial Pathogenesis Part A: Identification and Regulation of Virulence Factors ◽

10.1016/0076-6879(94)35182-1 ◽

1994 ◽

pp. 691-705 ◽

Cited By ~ 11

Author(s):

Bruce L. Kagan ◽

Yuri Sokolov

Keyword(s):

Lipid Bilayer ◽

Pore Formation ◽

Lipid Bilayer Membranes ◽

Bilayer Membranes

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Formation and stabilization of pores in bilayer membranes by peptide-like amphiphilic polymers

Soft Matter ◽

10.1039/c7sm02404e ◽

2018 ◽

Vol 14 (13) ◽

pp. 2526-2534 ◽

Cited By ~ 4

Author(s):

Ankush Checkervarty ◽

Marco Werner ◽

Jens-Uwe Sommer

Keyword(s):

Monte Carlo ◽

Monte Carlo Simulations ◽

Lipid Bilayer ◽

Pore Formation ◽

Amphiphilic Polymers ◽

Amphiphilic Copolymers ◽

Lipid Bilayer Membranes ◽

Bilayer Membranes ◽

Fluid Membrane ◽

Brush Model

We study pore formation in models of lipid bilayer membranes interacting with amphiphilic copolymers mimicking anti-microbial peptides using Monte Carlo simulations and we rationalize our results by a simple brush-model for the fluid membrane.

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