title: More than a pore: the cellular response to cholesterol-dependent cytolysins.
abstract: Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W. Medical Center Dr., Ann Arbor, MI 48109, USA. skbc@umich.edu
authors.forename: Sara K B
authors.initials: SK
authors.lastname: Cassidy
authors.forename: Mary X D
authors.initials: MX
authors.lastname: O'Riordan
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003603:Cytotoxins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004705:Endocytosis / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D015388:Organelles / Q000187:drug effects / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D013499:Surface Properties
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D052899:Pore Forming Cytotoxic Proteins; D002784:Cholesterol