Regulation of cell wall plasticity by nucleotide metabolism in Lactococcus lactis

To ensure optimal cell growth and separation, and to adapt to environmental parameters, bacteria have to maintain a balance between cell wall (CW) rigidity and flexibility. This can be achieved by a concerted action of peptidoglycan (PG) hydrolases and PG synthesizing/modifying enzymes. In a search for new regulatory mechanisms responsible for the maintenance of this equilibrium inLactococcus lactis, we isolated mutants that are resistant to the PG hydrolase lysozyme. We found that 14% of the causative mutations were mapped in theguaAgene, the product of which is involved in purine metabolism. Genetic and transcriptional analyses combined with PG structure determination of theguaAmutant enabled us to reveal the pivotal role of thepyrBgene in the regulation of CW rigidity. Our results indicate that conversion of L-aspartate (L-Asp) to N-carbamoyl-L-aspartate by PyrB may reduce the amount of L-Asp available for PG synthesis and thus cause the appearance of Asp/Asn-less stem peptides in PG. Such stem peptides do not form PG cross-bridges, resulting in a decrease in PG crosslinking and, consequently, reduced PG thickness and rigidity. We hypothesize that the concurrent utilization of L-Asp for pyrimidine and PG synthesis may be part of the regulatory scheme, ensuring CW flexibility during exponential growth and rigidity in stationary phase. The fact that L-Asp availability is dependent on nucleotide metabolism, which is tightly regulated in accordance with the growth rate, providesL. lactiscells the means to ensure optimal CW plasticity without the need to control the expression of PG synthesis genes