biostudies-literatureJohnstone BAState Government of VictoriaNIAID NIH HHSNational Health and Medical Research CouncilNational Institutes of HealthNIH HHSAustralian Research Council1169-1179https://www.ebi.ac.uk/biostudies/studies/S-EPMC9712165biostudies-literatureUnknown74(12)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.IUBMB lifeCholesterol-dependent cytolysins: The outstanding questions.PMC9712165R01 AI037657APP1194263R37 AI037657DP200102871R37-AI037657IC200100052DP160101874R37‐AI037657Christie MPWalsh JCBocking TMcGuiness CJohnstone BAParker MWTweten RKJoseph RMorton CJfalseCholesterol-dependent cytolysins: The outstanding questions.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.2022-01-01T00:00:00Z2022 Dec2025-05-29T21:47:22.779Z2025-02-19T01:17:31.095ZS-EPMC97121653583635810.1002/iub.2661