Abstract:All amino acids (AAs) other than glycine are chiral, existing in the forms of D-amino acids (DAAs) or L-amino acids (LAAs). Compared to widely studied LAAs, our knowledge about DAAs is still very limited. Herein, we review the advances in studying the physiological roles and functions of DAAs in bacteria. Though DAAs are not involved in protein synthesis, they are found in a wide range of organisms, especially bacteria. It is known that DAAs, especially non-canonical D-amino acids (NCDAAs), have a wide variety of special functions in bacterial physiology. As building blocks, DAAs are important components of peptidoglycan in bacterial cell wall, non-ribosomal peptides and poly-γ-glutamate. At the individual cell level, DAAs regulate bacterial surface charges and autolysin activity, inhibit the germination of bacterial spores, regulate cell wall remodeling during stationary phases and virulence of pathogenic bacteria. While at the population level, DAAs play important roles in biofilm development and bacterial ecology. Additionally, certain DAAs can support the growth of certain bacteria directly as nutrients, though some others act as inhibitors of bacterial growth.