D-Amino Acids Govern Stationary Phase Cell Wall Remodeling in Bacteria

Abstract

In all known organisms, amino acids are predominantly thought to be synthesized and used as their L-enantiomers. Here, we found that bacteria produce diverse D-amino acids as well, which accumulate at millimolar concentrations in supernatants of stationary phase cultures. In Vibrio cholerae, a dedicated racemase produced D-Met and D-Leu, while Bacillus subtilis generated D-Tyr and D-Phe. These unusual D-amino acids appear to modulate synthesis of peptidoglycan, a strong and elastic polymer that serves as the stress-bearing component of the bacterial cell wall. D-amino acids influenced peptidoglycan composition, amount, and strength, both via their incorporation into the polymer and by regulating enzymes that synthesize and modify it. Thus, synthesis of D-amino acids may be a common strategy for bacteria to adapt to changing environmental conditions.

d-Amino Acid Probes for Penicillin Binding Protein-based Bacterial Surface Labeling

“…Although there are a few examples of D-amino acids being generated and utilized in eukaryotic organisms, it was believed that its existence in bacteria was limited to being a building block for non-ribosomal peptide synthesis and the core component of the peptidoglycan. The discovery that many bacterial species are capable of generating diverse D-amino acids that are expelled into the surrounding medium suggests that this process may have specific physiological consequences (43,44). However, there has not been any conclusive physiological role assigned to peptidoglycan remodeling via unnatural D-amino acids.…”

Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway

“…This is thought to be of functional benefit to bacteria, since it provides resistance to mammalian proteases (17). In addition, bacteria can release D-isomers of amino acids (12). Recently, the ability of the intestinal microbiome to regulate liver inflammation was established and was due in part on the ability of bacterial components in the portal blood (7).…”

High-throughput, Highly Sensitive Analyses of Bacterial Morphogenesis Using Ultra Performance Liquid Chromatography

“…The Gram-negative bacterium V. cholerae has curved rod morphology, and HPLC analyses of strain N16961 previously detected shorter glycan strands than in E. coli (26,55,56). We performed a similar survey of morphology and peptidoglycan content from strains CA401, MO10, MZ02, MAK757, and 0139, which cover the El Tor (MO10, MAK757) and Classical (CA401) biogroups, and the O139 (MO10), O1 (CA401, MAK757), and non-O1, non-O139 (MZO2) serotypes.…”