A recent Science paper from the Waldor laboratory provides evidence that bacteria use D-amino acids to remodel the cell wall during the adaptation to stationary phase.
Almost all naturally occurring proteinogenic amino acids are chiral and, as such, can exist as L- and D-form mirror-image stereoisomers. In nature, L-forms predominate, and few biological functions have been assigned to D-amino acids. In bacteria, however, two D-amino acids, D-Ala and D-Glu, are incorporated into the cell wall peptidoglycan. Lam, Oh, Cava and colleagues were investigating cell wall synthesis in Vibrio cholerae when they noticed that V. cholerae cells with a mutation in one of the penicillin-binding proteins involved in peptidoglycan synthesis underwent an unusual morphological transition from rod-shaped to coccoid cells during stationary phase. This switch was controlled by a soluble factor or factors that are secreted into the culture supernatant. Fractionation of stationary-phase supernatants revealed the presence of d-amino acids, and a time course analysis showed that these amino acids accumulated in the supernatant to millimolar levels during stationary phase. D-Ala and D-Glu are known to be produced from their l-form enantiomers by an amino acid racemase. Lam et al. identified a gene encoding a periplasmic racemase in V. cholerae, vc1312, which they renamed bsrV (broad-spectrum racemase Vibrio). D-amino acid production in ΔbsrV cells was greatly reduced compared with production in wild-type cells.
As cells enter stationary phase they shut down unnecessary metabolic pathways. So why divert resources to the production of D-amino acids? The authors looked at the composition of the peptidoglycan in wild-type and ΔbsrV V. cholerae and found that, although there were no differences during exponential growth, ΔbsrV stationary-phase cells contained twice as much peptidoglycan as wild-type stationary-phase cells. There were also differences in peptidoglycan structure, and peptidoglycan from ΔbsrV cells was less resistant to osmotic stress than that from wild-type V. cholerae cells. The authors conclude that the production of D-amino acids by the BsrV racemase regulates the amount and composition of peptidoglycan in V. cholerae stationary-phase cells. The mechanisms involved remain to be fully determined, but high-performance liquid chromatography analysis revealed that D-Met could be incorporated into V. cholerae peptidoglycan. Further work suggested that D-amino acids might also regulate the activity of the penicillin-binding proteins that are responsible for peptidoglycan synthesis and modification.
Finally, Lam et al. showed that this phenomenon is not restricted to V. cholerae. The production of D-amino acids and the presence of putative racemases were observed in many other species, including Bacillus subtilis and Staphylococcus aureus . More detailed analysis of the effects of D-amino acid production on B. subtilis stationary-phase cultures showed that D-amino acids also downregulate peptidoglycan synthesis in this species.
These results suggest that bacteria use D-amino acids to regulate the cell wall remodelling that is required on entry to stationary phase, and the authors propose that D-amino acids could be used to synchronously control this process in a bacterial population. Further work is required to elucidate the details of the mechanisms involved, and this work shows that there is still much to be uncovered about the roles of D-amino acids in bacteria.
ORIGINAL RESEARCH PAPER
Lam, H. et al. D-Amino acids govern stationary phase cell wall remodelling in bacteria. Science 325, 1552–1555 (2009)
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Molloy, S. Mirror signal, manoeuvre. Nat Rev Microbiol 7, 759 (2009). https://doi.org/10.1038/nrmicro2250
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DOI: https://doi.org/10.1038/nrmicro2250