Cholesterol-dependent cytolysins: The outstanding questions.

Bronte A Johnstone, Riya Joseph, Michelle P Christie, Craig J Morton, Conall McGuiness, James C Walsh, Till Böcking, Rodney K Tweten, Michael W Parker

Journal: IUBMB life 2022;74(12):1169-1179

PMID: 35836358

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Abstract

The cholesterol-dependent cytolysins (CDCs) are a major family of bacterial pore-forming proteins secreted as virulence factors by Gram-positive bacterial species. CDCs are produced as soluble, monomeric proteins that bind specifically to cholesterol-rich membranes, where they oligomerize into ring-shaped pores of more than 30 monomers. Understanding the details of the steps the toxin undergoes in converting from monomer to a membrane-spanning pore is a continuing challenge. In this review we summarize what we know about CDCs and highlight the remaining outstanding questions that require answers to obtain a complete picture of how these toxins kill cells.

Address: Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.; EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.; Australian Cancer Research Foundation Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.

DOI: 10.1002/iub.2661

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https://assays.cancer.gov/CPTAC-43

MeSH Terms: Cytotoxins, Bacterial Toxins, Cholesterol, Bacteria, Cell Membrane, Bacterial Proteins