Aspartate aminotransferase is required forexpansion in the inflamed gut via TCA anaplerosis.

Abstract

Aspartate represents an important proteogenic amino acid in all living organisms. Many microorganisms can produce aspartate through various biosynthetic processes, utilizing it for energy production and as a precursor for synthesizing other biomolecules, such as amino acids and nucleotides. The enteric pathogenserovar Typhimurium (. Tm) has developed mechanisms to access aspartate as a nutrient source during expansion in the inflamed gut. However, how. Tm deals with aspartate starvation during infection remains unknown. To address this knowledge gap, we interrogated's reliance on the bidirectional aspartate aminotransferase encoded byfor growthand during host colonization using murine models ofinfection. AspC can interconvert aspartate and the TCA intermediate oxaloacetate and is hypothesized to support. Tm cellular demands for aspartate during starvation or support refueling of the TCA cycle via oxaloacetate synthesis. Herein, we find that loss ofresults in a gut-specific. Tm colonization defect that increases with the course of infection. Importantly,is dispensable for. Tm systemic colonization in CBA/J mice. Additionally, we report that loss ofresults in a significant growth defect during respiration of inflammation-derived electron acceptors. Interruption of oxidative TCA cycle progression via TCA enzyme deletion or supplementation with TCA intermediates (e.g., oxaloacetate) abrogates the defect observed in Δ. Tm, thus suggesting the requirement for AspC to catabolize aspartate and support the TCA cycle during respiration. Altogether, we report that AspC plays a critical role in. Tm pathogenesis in a gut-specific manner during inflammation through supporting energy generation.