Much of our research is directed at gaining a better understanding of T.pallidum metabolism. Understanding its growth requirements will facilitate so many aspects of syphilis research. Understanding of the T.pallidum physiology, structure, host immunity, antimicrobial susceptibility, and perhaps ultimately, could lead to new methods of syphilis control.
One of our biggest challenges is the presence of mammalian cells in the culture system. If we can determine what nutrients the cells are providing, we can remove them from the system and it would simplify it. That would allow us to have no contaminated mammalian cell DNA or protein, which would make the experimental analysis easier.
For over 100 years after its initial isolation, T.pallidum was propagated through infection of rabbits. The in vitro culture system allows you to avoid the use of animals and is more cost effective. It also allows for techniques such as genetic engineering that would not be possible in the animal model.
The availability of an in vitro culture method has already greatly expanded the number of groups studying Treponema pallidum. It has also led to advances such as the first mutagenesis of the organism, as well as high throughput screening of antibiotics for those useful in treating syphilis. In vitro culture has paved the way for the detailed analysis of T.pallidum growth requirements, gene function, and immune targets.
These questions are difficult, if not impossible, to address effectively using just the rabbit model. We hope that these approaches will help improve the diagnosis, treatment, and prevention of syphilis. In addition to our efforts to improve the in vitro cultivation system, we will focus on genetic manipulation of T.pallidum through transposon mutagenesis.
We hope to do a large scale functional screen to identify genes important in T.pallidum pathogenesis.
