The Comprehensive Sourcebook of Bacterial Protein Toxins

A significant number of bacteria, including the emerging multidrug-resistant “superbugs,” such as Pseudomonas aeruginosa, Clostridium difficile, Staphylococcus aureus, and Escherichia coli, secrete highly potent exotoxins with no antitoxins currently available to disable them. Several bacterial toxins, such as the botulinum neurotoxin (BoNT) of Clostridium botulinum, can be aerosolized and used as biological weapons directly. With some bacterial diseases, such as anthrax, flu-like symptoms appear only after bacteria have proliferated inside the host and have started to produce toxins that ultimately cause death [1]. Even though aggressive antibacterial treatment effectively inhibits Bacillus anthracis propagation, patients can still die because of intoxication [2]. Furthermore, several engineered strains of B. anthracis, which are resistant to the existing antibacterial agents, have already been developed [3,4]. Therefore, the discovery and development of small-molecule antitoxins represent a high-priority task in drug design, medicinal chemistry, and biodefense [4,5]. In the last ten years, a number of biophysical studies have focused on finding ways to disable those bacterial toxins which form ion channels in the host’s cell membranes. This chapter focuses on the existing efforts to design antitoxins that counteract channelforming bacterial toxins.