Axonally Transported Shigella Cytotoxin is Neuronotoxic

Abstract

Shigella dysenteriae strains produce an exotoxin (SdT) which inhibits protein synthesis in susceptible cells and is neurotoxic in some species. Intraneural microinjection of highly purified SdT into the cervical vagus nerves of rats, mice, guinea pigs and rabbits produced cytopathic changes within 24 hours in vagal sensory but not motor neurons. These changes consisted of an initial loss of Nissl substance followed by progressive cell degeneration and resulted in permanent neuronal loss. Indirect immunoperoxidase staining demonstrated SdT in nodose ganglion sensory neurons but not in vagal motor neurons of the brainstem. In rats, fatal enterotoxicity was common after intraneural injection of SdT doses that were reliably neuronotoxic; in rabbits and mice, a fatal ascending paralysis occurred at similar doses. Cytopathic changes were noted rarely in nodose sensory neurons of the uninjected side in mice suggesting systemic distribution and neuronal uptake of toxin. Injection of SdT into the tongue muscles of rats and mice failed to affect hypoglossal motor neurons within 50 hours. We conclude SdT is taken up and retrogradely transported by vagal sensory neurons with a resultant destruction of these neurons. The relationship of these findings to the reported neurotoxicity of SdT is unclear. However, SdT may prove useful in making selective lesions or as a model for some forms of neuronal degeneration.