(474b) Optimal Protein Allocation Controls the Inhibition of Glta and Acnb in Neisseria Gonorrhoeae

Neisseria gonorrhea (Gc), the causative agent of gonorrhea, is a global public health challenge noted for its capability to cause severe reproductive health complications. Understanding the metabolic niche of this pathogen is pivotal to comprehending its pathogenicity. Previous experimental observations indicated that N. gonorrhoeae turns off GltA (citrate synthase) and AcnB (aconitate hydratase) of the TCA cycle, despite having the capability to encode those proteins. However, the underlying cause of that is yet to be understood. This study investigates this phenomenon from the optimal protein allocation perspective. In this work, we used the recently published Gc metabolic model, iNgo_557, and incorporated protein cost (per flux) information into the model as a proteomic constraint. By integrating the proteomic constraint, we examined Gc's strategy for protein allocation under limited and high cellular protein availability. Our findings demonstrate that GltA and AcnB are deactivated when the cellular protein content is constrained. Furthermore, a shift towards oxidative fermentation from the TCA cycle after a specific growth rate is observed, which is consistent with the experimental observation. This shift is attributed to the higher proteomic efficiency of oxidative fermentation at higher glucose uptake rates compared to respiration. Surprisingly, increasing the protein content within our model activated GltA and AcnB and delayed the onset of oxidative fermentation, confirming that protein allocation is the key determinant in the metabolic phenotype observed in Gc. These insights underscore the importance of Gc's metabolic strategy from the protein allocation perspective, offering a blueprint for Gc's metabolic adaptation in different environments.