Carbon upshift in Lactococcus cremoris elicits immediate initiation of proteome-wide adaptation, coinciding with growth acceleration and pyruvate dissipation switching

Fitness optimization in a dynamic environment requires bacteria to adapt their proteome in a tightly regulated manner by altering protein production and/or degradation. Here, we investigate proteome adaptation in Lactococcus cremoris following a sudden nutrient upshift (e.g., nutrients that allow faster growth) and focus especially on the fate of redundant proteins after the shift. Protein turnover analysis demonstrated that L. cremoris cultures shifted from galactose to glucose, immediately accelerate growth and initiate proteome-wide adjustment toward glucose-optimized composition. Redundant proteins were predominantly adjusted by lowering (or stopping) protein production combined with dilution by growth. However, pyruvate formate lyase activator (PflA) was actively degraded, which appears correlated to reduced 4Fe-4S cofactor availability. Active PflA removal induces the shutdown of galactose-associated mixed acid fermentation to accelerate the switch toward glucose-associated homolactic fermentation. Our work deciphers molecular adjustments upon environmental change that drive physiological adaptation, including growth rate and central energy metabolism.