The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake in Streptococcus mutans

Pyruvate forms the central node of carbon metabolism and promotes growth as an alternative carbon source during starvation. We recently revealed that LrgAB functions as a stationary phase pyruvate uptake system in Streptococcus mutans, the primary causative agent of human dental caries, but its underlying regulatory mechanisms are still not clearly understood. This study was aimed at further characterizing the regulation of LrgAB from a metabolomic perspective. We utilized a series of GFP quantification, growth kinetics, and biochemical assays. We disclosed that LrgAB is critical for pyruvate uptake especially during growth under low-glucose stress. Inactivation of the Pta-Ack pathway, responsible for the conversion of acetyl-CoA to acetate, completely inhibits stationary phase lrgAB induction and pyruvate uptake, and renders cells insensitive to external pyruvate as a signal. Inactivation of Pfl, responsible for the conversion of pyruvate to acetyl-CoA under anaerobic conditions, also affected stationary phase pyruvate uptake. This study explores the metabolic components of pyruvate uptake regulation through LrgAB, and highlights its potential as a metabolic stimulator, contributing to the resuscitation and survival of S. mutans cells during nutritional stress.