Journal of Molecular Medicine

, Volume 91, Issue 10, pp 1131-1141

First online:

Retrograde trafficking of AB5 toxins: mechanisms to therapeutics

  • Somshuvra MukhopadhyayAffiliated withDivision of Pharmacology & Toxicology, College of Pharmacy and Institute for Cellular & Molecular Biology, The University of Texas at Austin
  • , Adam D. LinstedtAffiliated withDepartment of Biological Sciences, Carnegie Mellon University Email author 

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Bacterial AB5 toxins are a clinically relevant class of exotoxins that include several well-known members such as Shiga, cholera, and pertussis toxins. Infections with toxin-producing bacteria cause devastating human diseases that affect millions of individuals each year and have no definitive medical treatment. The molecular targets of AB5 toxins reside in the cytosol of infected cells, and the toxins reach the cytosol by trafficking through the retrograde membrane transport pathway that avoids degradative late endosomes and lysosomes. Focusing on Shiga toxin as the archetype member, we review recent advances in understanding the molecular mechanisms involved in the retrograde trafficking of AB5 toxins and highlight how these basic science advances are leading to the development of a promising new therapeutic approach based on inhibiting toxin transport.


Retrograde trafficking AB5 toxins Mechanisms Therapeutics