Bacterial Pathogenesis and Host-Pathogen Interactions
Science is revealing the truth about nature.
Bacterial Pathogenesis and Host-Pathogen Interactions
Our research is driven by an interest in bacterial pathogenesis and its relationship with microbial physiology, structure, and genetics. Treponema pallidum (the causative agent of syphilis) and Borrelia burgdorferi (which causes Lyme disease) are spirochetes that cause chronic, multisystemic diseases. These organisms can invade almost any tissue and survive and cause disease in the host for years to decades, and thus serve as important examples of persistent, invasive pathogens.
Long-term in vitro culture of Treponema pallidum
The culture of T. pallidum in vitro has been a research goal ever since its identification as the cause of syphilis in 1905. Our group recently described a system that supports the long-term multiplication of T. pallidum in a tissue culture system (Edmondson et al., 2018). We have now maintained exponential growth of T. pallidum for over three years and have embarked on an NIH-funded project to 1) optimize the tissue culture system, 2) delineate nutritional requirements and growth characteristics, with the goal of developing an axenic (cell-free) culture system, and 3) investigate the possibility of mutational analysis of T. pallidum. Other potential applications include the direct culture of T. pallidum from patient specimens and the use of this system for antimicrobial susceptibility testing.
Molecular genetics of Lyme disease pathogenesis
Molecular genetic techniques such as transposon mutagenesis (including signature tagged mutagenesis), PCR, Luminex®-based high-throughput screening procedures, and reverse genomics are being utilized in combination with infectivity studies to identify B. burgdorferi genes and gene products required for infectivity in a mouse model. Using such approaches, our group identified and characterized the vls antigenic variation system of B. burgdorferi, an elaborate mechanism similar to the Variable Major Protein system of relapsing fever borreliae. We have also utilized a global approach to identify additional genes encoding virulence determinants important in the pathogenesis of Lyme disease through the screening of a transposon mutant library using high-throughput approaches (including Tn-seq).
Ultrastructure of pathogenic spirochetes
Cryo-electron tomography, a relatively new electron microscopy technique that creates 3D images of bacteria, is being utilized in collaborative studies with Dr. Jun Liu at Yale University and Dr. Bo Hu at UTHealth Houston to elucidate the architecture of the flagellar motor and other structural elements of these organisms.