Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis

Solopova, Ana;Formosa, Cécile;Courtin, Pascal;Furlan, Sylviane;Kulakauskas, Saulius;et.al.
(2016) Journal of Biological Chemistry — Vol. 291, n° 21, p. 11323-11336 (2016)

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Authors
  • Solopova, Ana
    Author
  • Formosa, CécileUCLouvain
    Author
  • Courtin, Pascal
    Author
  • Furlan, Sylviane
    Author
  • Hols, Pascalorcid-logoUCLouvain
    Author
  • Author
  • Kulakauskas, Saulius
    Author
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Abstract
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 in Lactococcus lactis, we isolated mutants that are resistant to the PG hydrolase lysozyme. We found that 14% of the causative mutations were mapped in the guaA gene, the product of which is involved in purine metabolism. Genetic and transcriptional analyses combined with PG structure determination of the guaA mutant enabled us to reveal the pivotal role of the pyrB gene in the regulation ofCWrigidity.Ourresults indicate that conversion of L-aspartate (L-Asp) to N-carbamoyl-L-aspartate by PyrB may reduce the amount of L-Asp available forPGsynthesis 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 cross-linking and, consequently, reduced PG thickness and rigidity.Wehypothesize 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, provides L. lactis cells themeansto ensure optimalCWplasticity without theneedto control the expression of PG synthesis genes.
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Citations

Solopova, A., Formosa, C., Courtin, P., Furlan, S., Veiga, P., Péchoux, C., Armalyte, J., Sadauskas, M., Kok, J., Hols, P., Dufrêne, Y., Kuipers, O. P., Chapot-Chartier, M.-P., & Kulakauskas, S. (2016). Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis. Journal of Biological Chemistry, 291(21), 11323-11336. https://doi.org/10.1074/jbc.M116.714303 (Original work published 2016)