Emerging Role of D-Amino Acid Metabolism in the Innate Defense.

Jumpei Sasabe,Masataka Suzuki

doi:10.3389/fmicb.2018.00933

Abstract

Mammalian innate and adaptive immune systems use the pattern recognition receptors, such as toll-like receptors, to detect conserved bacterial and viral components. Bacteria synthesize diverse D-amino acids while eukaryotes and archaea generally produce two D-amino acids, raising the possibility that many of bacterial D-amino acids are bacteria-specific metabolites. Although D-amino acids have not been identified to bind to any known pattern recognition receptors, D-amino acids are enantioselectively recognized by some other receptors and enzymes including a flavoenzyme D-amino acid oxidase (DAO) in mammals. At host–microbe interfaces in the neutrophils and intestinal mucosa, DAO catalyzes oxidation of bacterial D-amino acids, such as D-alanine, and generates H2O2, which is linked to antimicrobial activity. Intestinal DAO also modifies the composition of microbiota through modulation of growth for some bacteria that are dependent on host nutrition. Furthermore, regulation and recognition of D-amino acids in mammals have additional meanings at various host–microbe interfaces; D-phenylalanine and D-tryptophan regulate chemotaxis of neutrophils through a G-coupled protein receptor, D-serine has a bacteriostatic role in the urinary tract, D-phenylalanine and D-leucine inhibit innate immunity through the sweet taste receptor in the upper airway, and D-tryptophan modulates immune tolerance in the lower airway. This mini-review highlights recent evidence supporting the hypothesis that D-amino acids are utilized as inter-kingdom communication at host–microbe interface to modulate bacterial colonization and host defense.

Highlights

Among all domains of life, bacteria have the largest capacity to produce wide variety of D-amino acids, whereas archaea and eukaryotes are thought to synthesize generally two kinds of D-amino acids, D-serine and D-aspartate
After discovery of D-amino acids as integral components of bacterial cell wall in 1950s, Cline and Lehrer in 1969 identified D-amino acid oxidase (DAO) activity in granule fraction of human neutrophilic leukocytes (Cline and Lehrer, 1969), which is linked to bactericidal activity of leukocytes by H2O2 produced through oxidation of bacterial D-amino acids (Eckstein et al, 1971; DeChatelet et al, 1972)
The first is the similar way as described in the leukocytes that oxidation of bacterial D-amino acids generates bactericidal H2O2, which limits colonization of pathogenic bacteria including Vibrio cholerae in the small intestine

Summary

Introduction

Among all domains of life, bacteria have the largest capacity to produce wide variety of D-amino acids, whereas archaea and eukaryotes are thought to synthesize generally two kinds of D-amino acids, D-serine and D-aspartate. After discovery of D-amino acids as integral components of bacterial cell wall in 1950s, Cline and Lehrer in 1969 identified DAO activity in granule fraction of human neutrophilic leukocytes (Cline and Lehrer, 1969), which is linked to bactericidal activity of leukocytes by H2O2 produced through oxidation of bacterial D-amino acids (Eckstein et al, 1971; DeChatelet et al, 1972). DAO was identified in epithelial surface of the mammalian small intestine, where interplay between mammalian DAO and bacterial D-amino acids modifies commensal bacteria and mucosal defense (Sasabe et al, 2016).

Results

Conclusion