Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, United States.
Pathog Dis. 2024 Feb 7;82. doi: 10.1093/femspd/ftae023.
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 Ngo's ability to encode tricarboxylic acid (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 toward acetate overflow for Adenosine triphosphate (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 Ngo's metabolic phenotype. These findings underscore the significance of Ngo's metabolic adaptation in light of optimal protein allocation, providing a blueprint to understand Ngo's metabolic landscape.
淋病奈瑟菌（Ngo）对全球公共卫生构成重大威胁，因其对生殖健康有严重影响。了解其代谢表型对于理解其致病性至关重要。尽管 Ngo 能够编码三羧酸（TCA）循环蛋白 GltA 和 AcnB，但它们的活性受到显著限制。为了研究这一现象，我们使用了 iNgo_557 代谢模型，并对总细胞蛋白含量进行了限制。我们的结果表明，低细胞蛋白含量严重限制了 GltA 和 AcnB 的活性，导致 ATP 生产偏向于乙酰酸盐溢出，这在蛋白利用方面更为高效。令人惊讶的是，增加细胞蛋白含量可缓解 GltA 和 AcnB 的这种限制，并延迟乙酰酸盐溢出的发生，这突出了蛋白分配作为理解 Ngo 代谢表型的关键决定因素。这些发现强调了 Ngo 代谢适应在最佳蛋白分配中的重要性，为理解 Ngo 的代谢景观提供了蓝图。
