A D-amino acid produced by plant-bacteria metabolic crosstalk empowers interspecies competition

The bacterial cell wall is made of peptidoglycan (PG), a polymer that is essential for maintenance of cell shape and survival. Many bacteria alter their PG chemistry as a strategy to adapt their cell wall to environmental challenges. Therefore, identifying these factors is important to better understand the interplay between microbes and their habitat. Here we used the soil bacterium Pseudomonas putida to uncover cell wall modulators from plant extracts and found canavanine (CAN), a non-proteinogenic amino acid. We demonstrated that cell wall chemical editing by CAN is licensed by P. putida BsrP, a broad-spectrum racemase which catalyzes production of D-CAN. Remarkably, D-CAN alters dramatically the PG structure of Rhizobiales (e.g. Agrobacterium tumefaciens, Sinorhizobium meliloti), impairing PG synthesis, crosslinkage and cell division. Using A. tumefaciens we demonstrated that the detrimental effect of D-CAN is suppressed by a single amino acid substitution in the cell division PG transpeptidase penicillin binding protein 3a. Collectively, this work provides a fascinating example of how interspecies metabolic crosstalk can be a source of novel cell wall regulatory molecules to govern microbial biodiversity.