Targeting Bacterial Toxins

Abstract

Protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. Lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin‐mediated pathogenicity. Despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. This Review presents the state of the art in bacterial toxin targeted drug development with a critical consideration of achieved breakthroughs and withstanding challenges. The discussion focuses on A–B‐type protein toxins secreted by four species of bacteria, namely Clostridium difficile (toxins A and B), Vibrio cholerae (cholera toxin), enterohemorrhagic Escherichia coli (Shiga toxin), and Bacillus anthracis (anthrax toxin), which are the causative agents of diseases for which treatments need to be improved.

Engineering red‐blood‐cell‐membrane–coated nanoparticles for broad biomedical applications

“…45 For instance, PFTs such as a-hemolysin and streptolysin-O require membrane interactions and oligomerizing actions with other toxin monomers for channel formation and cellular disruption. Nanoparticle detainment immobilizes the toxin molecules, alters their cellular distribution, and thus restrict their interactions with targeted cellular substrates.…”

Polymer antidotes for toxin sequestration

“…Although strictly speaking, toxins are of biological origin, similar challenges face the development of polymeric heavy metal sequestrants for use as antidotes to heavy metal poisoning, so recent findings in this area have also been included. Polymers capable of sequestering biological toxins have been included in a number of reviews [5][6][7], but these discussions were generally limited to selected polymers or toxins. Here we provide a more comprehensive evaluation of polymeric systems reported to be useful in neutralizing toxins.…”

“…A number of therapeutic strategies have been investigated to inhibit AB toxins at different points of pathogenesis [6]. Inhibiting the recognition and adhesion of the B subunit to the cell surface with polymers has become a particularly attractive option.…”

Update on non-O157 Shiga toxin-producing E. coli as a foodborne pathogen: analysis and control

“…The toxins are encoded by genes carried on lysogenic phages located in the STEC chromosome. Both toxins have an A 1 B 5 structure; the B moiety binds to globotriaosylceramide (Gb 3 ) present on host microvascular endothelial cell surfaces (kidney, intestine, and brain) followed by endocytosis of the toxin (Ivarsson et al ., 2012 ). The A subunit is released from the B moiety and enters the cytosol via chaperone-mediated transfer.…”