Enzyme-constrained metabolic model of <i>Treponema pallidum</i> identified glycerol-3-phosphate dehydrogenase as an alternate electron sink

This study advances our understanding of <i>Treponema pallidum</i>, the syphilis-causing pathogen, through the reconstruction of iTP251, the first genome-scale metabolic model for this organism, and its enzyme-constrained version, ec-iTP251. The work addresses the challenges of studying <i>T. pallidum</i>, an extracellular, host-adapted pathogen, due to its strict dependence on host-derived nutrients and challenges in <i>in vitro</i> cultivation. Validated with strong agreement to proteomics data, the model demonstrates high predictive reliability. Key insights include unique metabolic adaptations such as lactate uptake for ATP production and alternative redox-balancing mechanisms. These findings provide a robust framework for future studies aimed at unraveling the pathogen's survival strategies and identifying potential metabolic vulnerabilities.