Studies on the CDC-like pore-forming proteins. Our studies of the CDCs have recently led to our discovery of a large family of CDC-like pore-forming toxins (CDCLs), the genes of which are present in >300 species of bacteria that span ecological niches from the Saharan desert to the Arctic and Antarctic waters and are found in numerous important species of the human oral and colonic microbiomes. We employ a variety of biochemical and biophysical approaches to the study of the CDC mechanism. Although we have worked extensively on the CDC mechanism there still remain several intriguing aspects of their mechanisms that remain unknown. The mechanism by which they accomplish this transition is complex and each protein family contributes unique aspects to this process. The study of the CDC structure and pore-forming has led to our understanding of how human immune defense proteins, such as the complement membrane attack complex and perforin (MACPF) family of proteins, as well as a large class of protein toxins from poisonous marine fish, form their pores in the cell membrane An intriguing characteristic of these proteins is the ability of these proteins to make the transition from a soluble state to a homo-oligomeric pore-forming complex on the membrane. More than 100 bacteria species carry a gene for a CDC and they have been shown to play significant roles in the pathogenesis of such bacterial species as Clostridium perfringens (gas gangrene), Listeria monocytogenes (listeriosis), Streptococcus pneumoniae (pneumoniae, meningitis) and Streptococcus pyogenes (strep throat, necrotizing fasciitis). Over the past 30+ years our studies have primarily focused on the pore-forming mechanisms of a variety of toxins produced by a wide variety of pathogenic bacteria with an emphasis on the cholesterol dependent cytolysins (CDCs). Our research centers on the study of the mechanism of pore-forming toxins and proteins from prokaryotic and eukaryotic sources, although we have recently expanded into studies that involve an uncharacterized anti-bacterial toxin produced by certain species of the colonic microbiome. Studies on the Cholesterol-dependent Cytolysins (CDCs). Structural biology and biochemistry of bacterial protein toxins President’s Associates Presidential Professor, University of Oklahoma Health Sciences CenterĮndowed Professor, University of Oklahoma Health Sciences Center National Institute of Health (NIAID) Merit Award
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