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Retrograde trafficking of AB5 toxins: mechanisms to therapeutics

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Abstract

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.

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Acknowledgments

This study was supported by the National Institutes of Health grants R01 GM-084111 (to A.D.L.) and K99/R00 ES-020844 (to S.M.).

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  1. Division of Pharmacology & Toxicology, College of Pharmacy and Institute for Cellular & Molecular Biology, The University of Texas at Austin, Austin, TX, 78712, USA

    Somshuvra Mukhopadhyay

  2. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, 15213, USA

    Adam D. Linstedt

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Mukhopadhyay, S., Linstedt, A.D. Retrograde trafficking of AB5 toxins: mechanisms to therapeutics. J Mol Med 91, 1131–1141 (2013). https://doi.org/10.1007/s00109-013-1048-7

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