Molecular and cellular biology of bacterial lactate metabolism

Lactate is a key metabolite that is used as a carbon and energy source. It can also be generated as a metabolic end product, through reduction of pyruvate. Bacterial enzymes involved in lactate generation are classified as NAD⁺-dependent lactate dehydrogenases and are generally involved in production of lactate during fermentation, while NAD⁺-independent lactate dehydrogenases are involved in oxidation of lactate that is linked to reduction of quinone in respiratory or photosynthetic electron transport pathways, or in anaerobic lactate oxidation linked to electron bifurcation during heterotrophic growth. Enzymes specific for D-lactate, L-lactate or both stereoisomers exist and interconversion of D- and L- stereoisomers is catalyzed by a lactate racemase. Expression of operons encoding enzymes and transporters involved in lactate metabolism is regulated in several ways that can include sensing of the presence of L- or D- lactate by transcriptional regulators, control of gene expression through global regulators of carbon metabolism and regulators that respond to iron availability. Sensing of lactate also appears to be an important cue for changes in cell physiology and behavior and in some bacteria it has been shown to influence biofilm formation. Lactate plays a key role in the maintenance of human microbiomes in different niches and dysbiosis is often a result of an imbalance between lactate production and lactate consumption, which is linked to certain pathologies. Lactate is also an important carbon source for some bacterial pathogens and L-lactate has been shown to play a role in the pathogenesis in animal models of infection. Additionally, L-lactate produced by macrophages, neutrophils and epithelial cells may provide an important carbon source of the survival and growth of intracellular pathogens. Understanding of lactate metabolism at the biochemical, cellular and organismal/community level is of major importance in understanding and management of health and disease and in understanding environmental processes.