Pathogenic bacterial toxins can be repurposed as therapeutics. Binary bacterial toxins are macromolecular complexes that are a current focus of therapeutic development. These proteins bind to surfaces of specific human cell populations and transport enzymes across membranes. Basic research has characterized bacterial toxin mechanisms and structure so that protein domains can be “shuffled” for a variety of applications. This approach delivers an already characterized enzyme to new cell types, specified by binding affinity. Separated protein components from holotoxins are also repurposed into drug delivery applications to form composite multifunctional drug delivery units. Enzymatic domains are used for cancer diagnosis and treatment, influence of intracellular trafficking, and for providing relief from pain, autonomic disorders, movement disorders, spasticity, and HIV. Technical challenges to this field are the immunogenicity, solubility and stability of therapeutic fusion proteins. Clinical intervention and predictive computational approaches identify, prevent, and remove known and predicted immunogenicity without a significant loss of efficacy. Unrealized medical potential exists in a wealth of bacterial diversity that may be captured by the repurposing of bacterial toxins.
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