AspA activity orchestrates a growth-stress survival trade-off in Yersinia pestis via metabolic reprogramming.

In Yersinia pestis, the aspA codon 363 polymorphism links the GTG (AspA-active) allele to faster growth and higher ATP, while TTG (AspA-inactive) improves survival under nutrient limitation and multiple stresses.

• Why it matters: The mechanism behind an environment-dependent fitness trade-off driven by aspA polymorphism is unclear, despite Y. pestis facing oxidative, anaerobic, and hyperosmotic stresses during transmission.
• What they did: The study compared TTG and GTG strains for growth, ATP, and stress survival, used exogenous aspartate to test stress-specific effects, and performed 13C-labeled metabolic flux analysis to map aspartate fate and TCA flux.
• The result: GTG rapidly converts aspartate to fumarate to fuel the TCA cycle and boost ATP, whereas TTG stalls aspartate utilization and accumulates amino acids and lipids; adding TCA intermediates (fumarate, succinate, or malate) partially rescues TTG growth.