Protein toxins from plants and bacteria: Probes for intracellular transport and tools in medicine

Abstract

a b s t r a c tA number of protein toxins produced by bacteria and plants enter eukaryotic cells and inhibit protein synthesis enzymatically. These toxins include the plant toxin ricin and the bacterial toxin Shiga toxin, which we will focus on in this article. Although a threat to human health, toxins are valuable tools to discover and characterize cellular processes such as endocytosis and intracellular transport. Bacterial infections associated with toxin production are a problem worldwide. Increased knowledge about toxins is important to prevent and treat these diseases in an optimal way. Interestingly, toxins can be used for diagnosis and treatment of cancer.

Lipid-Mediated Endocytosis

“…A detailed discussion of the literature describing these phenomenona can be found in recent reviews (Chinnapen et al 2007;Johannes and Romer 2010;Sandvig et al 2010). STX reaches peripheral EEs 5 min, perinuclear EEs in 10 -20 min, TGN and Golgi complex in 30 -45 min, and the ER in 180 min or longer (McKenzie et al 2009).…”

“…Unlike other toxins and viruses that use cell surface proteins as their receptors, those that bind to glycosphingolipids are special because they are usually transported to the endoplasmic reticulum (ER) from where they penetrate into the cytosol. Once in the cytosol, the bacterial toxins and plant lectins manifest their toxicity by interfering with critical cell functions such as protein translation and regulation of membrane traffic (Sandvig et al 2010). The viruses take over the cellular machinery for their own replication.…”

Comprendre et combattre les toxines A/B en décryptant leur transport intracellulaire

“…Il a ainsi été montré que l'alun active certains récepteurs de l'immunité innée [4] ainsi que la libération de signaux endogènes tels que de l'acide urique [5]. L'alun est donc loin d'être immunologiquement inerte, et on peut même envisager que, comme pour les autres molécules adjuvantes connues [2], il agisse via l'activation de l'immunité innée. Nous nous sommes intéressés, chez la souris, à la composition des dépôts d'alun qui se forment rapidement localement après injection.…”

Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

“…In particular, several toxins (eg, ricin, shiga, and anthrax) were translocated into the Golgi or ER after endolysosomal trafficking (eg, EE, LE, and Lys), and then secreted outside by secretory pathway ( Figure 5). [125][126][127] The exocytosis mechanism of various NPs has not yet been fully understood, in contrast to endocytosis mechanisms. 88,128,129 Recent reviews reported the exocytosis of internalized NPs with respect to various physiochemical factors such as size, shape, and surface chemistry.…”