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dc.contributor.authorAbeyawardhane, D.L.
dc.contributor.authorGodoy-Ruiz, R.
dc.contributor.authorAdipietro, K.A.
dc.contributor.authorVarney, K.M.
dc.contributor.authorRustandi, R.R.
dc.contributor.authorPozharski, E.
dc.contributor.authorWeber, D.J.
dc.date.accessioned2021-04-12T16:16:43Z
dc.date.available2021-04-12T16:16:43Z
dc.date.issued2021-03-13
dc.identifier.urihttp://hdl.handle.net/10713/15194
dc.description.abstractNovel therapeutics are needed to treat pathologies associated with the Clostridioides difficile binary toxin (CDT), particularly when C. difficile infection (CDI) occurs in the elderly or in hospitalized patients having illnesses, in addition to CDI, such as cancer. While therapies are available to block toxicities associated with the large clostridial toxins (TcdA and TcdB) in this nosocomial disease, nothing is available yet to treat toxicities arising from strains of CDI having the binary toxin. Like other binary toxins, the active CDTa catalytic subunit of CDT is delivered into host cells together with an oligomeric assembly of CDTb subunits via host cell receptor-mediated endocytosis. Once CDT arrives in the host cell's cytoplasm, CDTa catalyzes the ADP-ribosylation of G-actin leading to degradation of the cytoskeleton and rapid cell death. Although a detailed molecular mechanism for CDT entry and host cell toxicity is not yet fully established, structural and functional resemblances to other binary toxins are described. Additionally, unique conformational assemblies of individual CDT components are highlighted herein to refine our mechanistic understanding of this deadly toxin as is needed to develop effective new therapeutic strategies for treating some of the most hypervirulent and lethal strains of CDT-containing strains of CDI. Copyright 2021 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorshipFunding: This research was funded by the state of Maryland.en_US
dc.description.urihttps://doi.org/10.3390/ijms22062926en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.subjectBinary toxinen_US
dc.subjectCDTen_US
dc.subjectCDTaen_US
dc.subjectCDTben_US
dc.subjectClostridioides difficileen_US
dc.subjectInfectious diseaseen_US
dc.subjectProtein structural biologyen_US
dc.titleThe importance of therapeutically targeting the binary toxin from clostridioides difficileen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ijms22062926


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