Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry

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Cytolethal distending toxins (CDTs) are produced by several bacterial pathogens and increase the ability of these bacteria to cause disease. After being taken up by host cells, CDTs are trafficked to the endoplasmic reticulum (ER) where they must translocate across the ER membrane to gain access to their intracellular target; however, this translocation process is poorly understood for CDTs. Here we provide evidence that CDTs require components of the ER-associated degradation (ERAD) pathway, a normal cellular process utilized to translocate terminally misfolded ER lumenal and membrane proteins across the ER membrane for degradation in the cytosol. Deletion of a key member of this pathway, Derl2, makes cells resistant to multiple CDTs. Interestingly, two domains within Derl2 which are required for ERAD of misfolded proteins are dispensable for intoxication by CDT. Further, we report two previously uncharacterized domains within Derl2 that are each required for intoxication. Consistent with a role of Derl2, abrogation of two other members of the ERAD pathway, Hrd1 and p97, results in retention of CDT in the ER and resistance to intoxication. Taken together, these data provide novel insight into how CDTs exit the ER and therefore gain access to their cellular targets.

Vyšlo v časopise: Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004295
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004295

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