Perfringolysin O-Induced Plasma Membrane Pores Trigger Actomyosin Remodeling and Endoplasmic Reticulum Redistribution.
Cláudia BritoFrancisco Sarmento MesquitaChristopher K E BleckJames R SellersDidier CabanesSandra SousaPublished in: Toxins (2019)
Clostridium perfringens produces an arsenal of toxins that act together to cause severe infections in humans and livestock animals. Perfringolysin O (PFO) is a cholesterol-dependent pore-forming toxin encoded in the chromosome of virtually all C. perfringens strains and acts in synergy with other toxins to determine the outcome of the infection. However, its individual contribution to the disease is poorly understood. Here, we intoxicated human epithelial and endothelial cells with purified PFO to evaluate the host cytoskeletal responses to PFO-induced damage. We found that, at sub-lytic concentrations, PFO induces a profound reorganization of the actomyosin cytoskeleton culminating into the assembly of well-defined cortical actomyosin structures at sites of plasma membrane (PM) remodeling. The assembly of such structures occurs concomitantly with the loss of the PM integrity and requires pore-formation, calcium influx, and myosin II activity. The recovery from the PM damage occurs simultaneously with the disassembly of cortical structures. PFO also targets the endoplasmic reticulum (ER) by inducing its disruption and vacuolation. ER-enriched vacuoles were detected at the cell cortex within the PFO-induced actomyosin structures. These cellular events suggest the targeting of the endothelium integrity at early stages of C. perfringens infection, in which secreted PFO is at sub-lytic concentrations.
Keyphrases
- endoplasmic reticulum
- endothelial cells
- high glucose
- particulate matter
- diabetic rats
- air pollution
- high resolution
- escherichia coli
- oxidative stress
- drug induced
- heavy metals
- single cell
- autism spectrum disorder
- polycyclic aromatic hydrocarbons
- stem cells
- mesenchymal stem cells
- breast cancer cells
- mass spectrometry
- induced pluripotent stem cells