Cyclic-di-AMP signalling in lactic acid bacteria.

Cyclic-di-AMP is a nucleotide second messenger present in Gram-positive bacteria and some Gram-negative bacteria and Archaea. The intracellular concentration of cyclic-di-AMP is adjusted in response to environmental and cellular cues, primarily through the activities of synthesis and degradation enzymes. It performs its role by binding to protein and riboswitch receptors, many of which contribute to osmoregulation. Imbalances in cyclic-di-AMP can lead to pleiotropic phenotypes, affecting aspects such as growth, biofilm formation, virulence and resistance to osmotic, acid and antibiotic stressors. This review focuses on cyclic-di-AMP signalling in lactic acid bacteria (LAB) incorporating recent experimental discoveries and presenting an analysis of signalling components from a variety of LAB including those found in food, and commensal, probiotic and pathogenic species. All LAB possess enzymes for the synthesis and degradation of cyclic-di-AMP, but they are highly variable with regards to the receptors they possess. Studies in Lactococcus and Streptococcus have revealed a conserved function for c-di-AMP in inhibiting the transport of potassium and glycine betaine, either through direct binding to transporters or to a transcriptional regulator. Structural analysis of several cyclic-di-AMP receptors from LAB has also provided insights into how this nucleotide exerts its influence.