Exploring Metabolic Adaptations in Treponema Pallidum through Genome-Scale Metabolic Modeling

Treponema pallidum, the causative agent of syphilis, exhibits unique metabolic characteristics, including the absence of a fully functional TCA cycle, which raises questions about how it sustains its high motility with limited ATP production. Moreover, T. pallidum is difficult to culture in vitro This project aims to reconstruct a genome-scale metabolic model (GEM) of T. pallidum to gain a better understanding of the bacteria, specifically addressing how it achieves high motility with limited ATP generation and whether its uptakes lactate as a carbon source to compensate for its lack of TCA cycle. To build this model, we first conducted a literature review to elucidate the bacterium's metabolism. Using Kbase, we drafted an initial model refined by adding and removing reactions to accurately represent T. pallidum's metabolic traits. After developing the model, we validated it using Memote, achieving a score of 92%. To further validate the model, we predicted the essential genes for T. pallidum. Since no information on T. pallidum's essential genes is available, we used BLAST to compare the predicted genes with those of E. coli and Neisseria gonorrhoeae. BLAST revealed that 41 out of the 42 predicted genes had orthologs in E. coli, and 37 had orthologs in N. gonorrhea. Of the E. coli orthologs, 26 were essential for growth, while 28 orthologs were essential in N. gonorrhea, further demonstrating the robustness of our model. Additionally, we used transport DB to verify the transporter proteins and tested the model's ability to metabolize various carbon sources such as glucose, pyruvate, and mannose. The resulting GEM provides insights into T. pallidum's metabolism and offers a foundation to explore key questions about the bacteria's high motility and its potential to uptake lactate as a carbon source. In the future, it can serve as a powerful tool for studying the bacterium's metabolic adaptations and responses to various environmental conditions.