Optimal Protein Allocation Controls the Inhibition of GltA and AcnB in Neisseria gonorrhoeae

Abstract

Neisseria gonorrhea (Ngo) is a major concern for global public health due to its severe implications for reproductive health. Understanding its metabolic phenotype is crucial for comprehending its pathogenicity. Despite Ngos ability to encode TCA cycle proteins, GltA and AcnB, their activities are notably restricted. To investigate this phenomenon, we used the iNgo_557 metabolic model and incorporated a constraint on total cellular protein content. Our results indicate that low cellular protein content severely limits GltA and AcnB activity, leading to a shift towards acetate overflow for ATP production, which is more efficient in terms of protein usage. Surprisingly, increasing cellular protein content alleviates this restriction on GltA and AcnB and delays the onset of acetate overflow, highlighting protein allocation as a critical determinant in understanding Ngos metabolic phenotype. These findings underscore the significance of Ngos metabolic adaptation in light of optimal protein allocation, providing a blueprint to understand Ngos metabolic landscape.