Structural and Functional Insights into the Delivery Systems of Bacillus and Clostridial Binary Toxins
Author:
Sevdalis Spiridon E.123ORCID, Varney Kristen M.123ORCID, Cook Mary E.13ORCID, Gillespie Joseph J.4, Pozharski Edwin123ORCID, Weber David J.123ORCID
Affiliation:
1. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 2. Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA 3. The Center for Biomolecular Therapeutics, The University of Maryland School of Medicine, Baltimore, MD 21201, USA 4. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Abstract
Pathogenic Bacillus and clostridial (i.e., Clostridium and Clostridioides) bacteria express a diverse repertoire of effector proteins to promote disease. This includes production of binary toxins, which enter host epithelial cells and seriously damage the intestinal tracts of insects, animals, and humans. In particular, binary toxins form an AB-type complex composed of a catalytic subunit that is toxic (A) and an oligomeric cell-binding and delivery subunit (B), where upon delivery of A into the cytoplasm of the host cell it catalytically ADP-ribosylates actin and rapidly induces host cell death. In this review, binary toxins expressed by Bacillus thuringiensis, Clostridioides difficile, and Clostridium perfringens will be discussed, with particular focus placed upon the structural elucidations of their respective B subunits and how these findings help to deconvolute how toxic enzyme delivery into target host cells is achieved by these deadly bacteria.
Funder
National Institute of Health
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