Dynamic response of catabolic pathways to autoacidification in Lactococcus lactis: transcript profiling and stability in relation to metabolic and energetic constraints.

The dynamic response of the central metabolic pathways to autoacidification (accumulation of organic acid fermentation products) in Lactococcus lactis was investigated in a global manner by integrating molecular data (cellular transcript concentrations, mRNA turnover) within physiological investigations of metabolic and energetic parameters. The decrease in pH associated with the accumulation of organic acids modified the physiological state of the cell considerably. Cytoplasmic acidification led to inhibition of enzyme activities and, consequently, to a diminished catabolic flux through glycolysis and a decreased rate of biochemical energy synthesis. This decrease in energy production together with the increased energy expenditure to counter cytoplasmic acidification led to energetic limitations for biomass synthesis. In these conditions, the specific growth rate decreased progressively, and growth ultimately stopped, although a diminished catabolic flux was maintained in the absence of growth. The cellular response to this phenomenon was to maintain significant levels of mRNA of catabolic genes, involving both continued transcription of the genes and also, in certain cases, an increase in transcript stability. Thus, translation was maintained, and intracellular concentration of certain enzymes increased, partially compensating for the inhibition of activity provoked by the diminished pH. When catabolic activity ceased after prolonged exposure to stress-induced stationary phase, endogenous RNA catabolism was observed.