Membrane Activity and Channel Formation of the Adenylate Cyclase Toxin (CyaA) of <i>Bordetella pertussis</i> in Lipid Bilayer Membranes
The Gram-negative bacterium <i>Bordetella pertussis</i> 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 repe...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/12/3/169 |
| Summary: | The Gram-negative bacterium <i>Bordetella pertussis</i> 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 Ca<sup>2+</sup> concentration with a half saturation constant of about 2 to 4 mM. |
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| ISSN: | 2072-6651 |