Preferred hexoses influence long-term memory and induction of lactose catabolism byStreptococcus mutans

Abstract

ABSTRACTBacteria prioritize sugar metabolism via carbohydrate catabolite repression, which regulates global gene expression to optimize the catabolism of preferred substrates. Here, we report an unusual long-term memory effect in certainStreptococcus mutansstrains that alters adaptation to growth on lactose after prior exposure to glucose or fructose. In strain GS-5, cells that were first cultured on fructose then transferred to lactose displayed an exceptionally long lag (>11 h) and slower growth, compared to cells first cultured on glucose or cellobiose, which displayed a reduction in lag phase by as much as 10 h. Mutants lacking the cellobiose-PTS or phospho-β-glucosidase lost the accelerated growth on lactose associated with prior culturing on glucose. The memory effects of glucose or fructose on lactose catabolism were not as profound in strain UA159, but the lag phase was considerably shorter in mutants lacking the glucose-PTS EIIMan. Interestingly, whenS.mutanswas cultivated on lactose, significant quantities of free glucose accumulated in the medium, with higher levels found in the cultures of strains lacking EIIMan, glucokinase, or both. Free glucose was also detected in cultures that were utilizing cellobiose or trehalose, albeit at lower levels. Such release of hexoses byS.mutansis likely of biological significance as it was found that cells required small amounts of glucose or other preferred carbohydrates to initiate efficient growth on lactose. These findings suggest thatS.mutansmodulates the induction of lactose utilization based on its prior exposure to glucose or fructose, which can be liberated from common disaccharides.IMPORTANCEUnderstanding the molecular mechanisms employed by oral bacteria to control sugar metabolism is key to developing novel therapies for management of dental caries and other oral diseases. Lactose is a naturally occurring disaccharide that is abundant in dairy products and commonly ingested by humans. However, for the dental caries pathogenStreptococcus mutans, relatively little is known about the molecular mechanisms that regulate expression of genes required for lactose uptake and catabolism. Two peculiarities of lactose utilization byS.mutansare explored here: a)S.mutansexcretes glucose that it cleaves from lactose and b) prior exposure to certain carbohydrates can result in a long-term inability to use lactose. The study begins to shed light on howS.mutansmay bet-hedge to optimize its persistence and virulence in the human oral cavity.