The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile

Novel therapeutics are needed to treat pathologies associated with the binary toxin (CDT), particularly when 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 l...

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Veröffentlicht in:International journal of molecular sciences 2021-03, Vol.22 (6), p.2926
Hauptverfasser: Abeyawardhane, Dinendra L, Godoy-Ruiz, Raquel, Adipietro, Kaylin A, Varney, Kristen M, Rustandi, Richard R, Pozharski, Edwin, Weber, David J
Format: Artikel
Sprache:eng
Schlagworte:
CDT
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Zusammenfassung:Novel therapeutics are needed to treat pathologies associated with the binary toxin (CDT), particularly when 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22062926