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Membrane Permeabilization by Pore-Forming RTX Toxins: What Kind of Lesions Do These Toxins Form?

Departamento de Bioquímica y Biología Molecular (UPV/EHU) and Instituto Biofisika (UPV/EHU, CSIC), Aptdo. 644, 48080 Bilbao, Spain
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Toxins 2019, 11(6), 354; https://doi.org/10.3390/toxins11060354
Received: 13 May 2019 / Revised: 12 June 2019 / Accepted: 16 June 2019 / Published: 18 June 2019
(This article belongs to the Special Issue Pore-Forming Toxins (PFTs): Never Out of Fashion)
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Abstract

Pore-forming toxins (PFTs) form nanoscale pores across target membranes causing cell death. The pore-forming cytolysins of the RTX (repeats in toxin) family belong to a steadily increasing family of proteins characterized by having in their primary sequences a number of glycine- and aspartate-rich nonapeptide repeats. They are secreted by a variety of Gram-negative bacteria and form ion-permeable pores in several cell types, such as immune cells, epithelial cells, or erythrocytes. Pore-formation by RTX-toxins leads to the dissipation of ionic gradients and membrane potential across the cytoplasmic membrane of target cells, which results in cell death. The pores formed in lipid bilayers by the RTX-toxins share some common properties such as cation selectivity and voltage-dependence. Hemolytic and cytolytic RTX-toxins are important virulence factors in the pathogenesis of the producing bacteria. And hence, understanding the function of these proteins at the molecular level is critical to elucidating their role in disease processes. In this review we summarize the current state of knowledge on pore-formation by RTX toxins, and include recent results from our own laboratory regarding the pore-forming activity of adenylate cyclase toxin (ACT or CyaA), a large protein toxin secreted by Bordetella pertussis, the bacterium causative of whooping cough. View Full-Text
Keywords: pore-forming proteins; Gram-negative bacteria; bacterial protein toxins; RTX toxins; toroidal pores pore-forming proteins; Gram-negative bacteria; bacterial protein toxins; RTX toxins; toroidal pores
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Ostolaza, H.; González-Bullón, D.; Uribe, K.B.; Martín, C.; Amuategi, J.; Fernandez-Martínez, X. Membrane Permeabilization by Pore-Forming RTX Toxins: What Kind of Lesions Do These Toxins Form? Toxins 2019, 11, 354.

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