Basic Science Departments | College of Medicine

Primary Faculty

Rodney K. Tweten, PhD

Rodney Tweten, PhD

George Lynn Cross Research Professor

Education:

Ph.D.: 1982, Kansas State University

Awards and Honors:

 

George Lynn Cross Professor

National Institute of Health (NIAID) Merit Award

Fellow, American Academy of Microbiology

President’s Associates Presidential Professor, University of Oklahoma Health Sciences Center

Endowed Professor, University of Oklahoma Health Sciences Center

Pre-OUHSC:

University of California at Los Angeles

Research Interests:

Structural biology and biochemistry of bacterial protein toxins

Teaching:

Basic Bacteriology

Contact Information:

Office: BRC 309

Email: Rodney-Tweten@ouhsc.edu

Research Interests:

Studies 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. 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). 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). 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. The mechanism by which they accomplish this transition is complex and each protein family contributes unique aspects to this process. Although we have worked extensively on the CDC mechanism there still remain several intriguing aspects of their mechanisms that remain unknown. We employ a variety of biochemical and biophysical approaches to the study of the CDC mechanism.

 

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. Our initial studies indicate that they are distant relatives of the CDCs and their targets are unknown, as their binding domains are evolutionary distinct from that of the CDCs, as well as each other. Furthermore, many of these CDCLs from the human colonic microbiome species, as well as the gut microbiomes of insects, have evolved what appears to be a two component pore complex, which is distinct from that of the CDCs.  Hence, the study of these CDC-like proteins is just beginning and will likely lead to a new frontier of study to understand how these proteins assemble a pore and their cellular targets.

 

Bacteroidetes anti-bacterial toxin. Our last project also involves a new field of study of, thus far, a unique antibacterial toxin produced by species of Bacteroides and Prevotella present in the human gut and oral microbiomes. This study is a collaboration with Dr. Laurie Comstock (University of Chicago). The mechanism of this toxin remains unknown and it has no analogs that suggest how it functions to kill or arrest microbial growth. We have determined that two proteolytic cleavage sites must be cleaved in sequence to activate the toxin and have identified its receptor on susceptible cells. Our future studies will be primarily focused on determining its structure, the mechanism of its activation and the mechanism by which it kills/inhibits susceptible bacterial species.

 

Current Lab Personnel:

Casie Collamore, Ph.D.

Tristan Sanford, Graduate Student

Hunter Abrahamsen, Graduate Student

Patricia Parrish,  Research Technician

Selected Publications:



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