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The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile

1
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2
Baltimore—Institute for Bioscience and Biotechnology Research, University of Maryland-Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA
3
The Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4
Merck & Co., Inc., Kenilworth, NJ 07033, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Carla Fiorentini
Int. J. Mol. Sci. 2021, 22(6), 2926; https://doi.org/10.3390/ijms22062926
Received: 25 November 2020 / Revised: 3 March 2021 / Accepted: 9 March 2021 / Published: 13 March 2021
(This article belongs to the Special Issue Bacterial Protein Toxins: Enemies within or Unexpected Friends 2.0)
Novel 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. View Full-Text
Keywords: Clostridioides difficile; binary toxin; infectious disease; protein structural biology; CDT; CDTa; CDTb Clostridioides difficile; binary toxin; infectious disease; protein structural biology; CDT; CDTa; CDTb
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MDPI and ACS Style

Abeyawardhane, D.L.; Godoy-Ruiz, R.; Adipietro, K.A.; Varney, K.M.; Rustandi, R.R.; Pozharski, E.; Weber, D.J. The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile. Int. J. Mol. Sci. 2021, 22, 2926. https://doi.org/10.3390/ijms22062926

AMA Style

Abeyawardhane DL, Godoy-Ruiz R, Adipietro KA, Varney KM, Rustandi RR, Pozharski E, Weber DJ. The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile. International Journal of Molecular Sciences. 2021; 22(6):2926. https://doi.org/10.3390/ijms22062926

Chicago/Turabian Style

Abeyawardhane, Dinendra L., Raquel Godoy-Ruiz, Kaylin A. Adipietro, Kristen M. Varney, Richard R. Rustandi, Edwin Pozharski, and David J. Weber 2021. "The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile" International Journal of Molecular Sciences 22, no. 6: 2926. https://doi.org/10.3390/ijms22062926

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