Charles Turnbough, Ph.D., professor emeritus in the UAB Department of Microbiology, has been selected as a recipient of the National Institute of Health (NIH) R21 Grant for his study, “Describing the stable, non-covalent BclA-BxpB attachment in B. anthracis spores."

This study examines the structure and assembly of the outermost protective layer of the B. anthracis spore, the causative agent of the potentially lethal disease anthrax.

This outer layer is called the exosporium, and it plays key roles in spore survival and infectivity of mammalian hosts.

Here, Turnbough explains the research that will be supported by the grant and his goals for the study.

Can you provide an overview of the specific research?

Turnbough: The bacterium Bacillus anthracis, the causative agent of anthrax, forms dormant spores highly resistant to harsh chemical and physical conditions. These spores can persist for many years in the soil and then quickly germinate and grow as vegetative cells when exposed to a nutrient-rich aqueous environment, which includes a human host. B. anthracis spores are of particular interest because they are used as agents of biological warfare and terrorism. For over two decades, in collaboration with several colleagues from UAB, my laboratory has discovered numerous exosporium proteins, deciphered their biological roles, and investigated how they assemble.

How will the NIH R21 grant facilitate your research efforts?

Turnbough: The R21 grant will provide a total funding of $386,100 over two years, starting on May 14, 2024, and ending on March 31, 2026. These funds are designated to cover expenses for personnel, supplies, and core facilities essential for our research endeavors.

What motivated you to pursue this specific area of research?

Turnbough: In 1996, I was asked to participate in a Department of Defense-sponsored project to develop detectors for B. anthracis spores, weaponized by the USSR and Russia. In particular, I was tasked with identifying molecules/ligands that could bind tightly and specifically to the surface of B. anthracis spores. My colleague Dr. John Kearney and I were successful in doing this, and these ligands were subsequently incorporated into the first commercial detectors for B. anthracis spores. Subsequently, Dr. Kearney and I began to examine the molecules in the exosporium to which our ligands bound. This began a long-term project, along with another UAB colleague, Dr. David Pritchard, to understand the exosporium's composition, structure, and function.

What methodologies or techniques will you be using in your research?

Turnbough: To describe the BclA-BxpB bond, we aim to create stable complexes between BxpB and the amino-terminal domain of BclA, the only region of BclA necessary for complex formation. The structure of the complex will be determined by X-ray crystallography and verified by other biophysical methods and mutational analysis of critical regions of each protein. For X-ray crystallography, we will collaborate with Dr. Todd Green, an associate professor in the Department of Microbiology, and Dr. Norbert Schormann, a facility manager and research scientist at UAB Structural Biology and X-RAY Crystallography Shared Facility.

What possible impacts could your research findings have on both the scientific community and public health?

Turnbough: The significance of our research extends widely, as numerous pathogenic bacterial spores exhibit an exosporium structure similar to that of B. anthracis. Likely, the external collagen-like proteins on these other spores are tightly attached by a mechanism analogous to the one we are investigating. Evidence indicates that the BclA homologs of other spores play critical roles in disease. The more we understand the structure and function of critical exosporium proteins like BclA, the better prepared we will be to respond to the adverse effects of disease-causing spores.