title: Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis.
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 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 cross-linking 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, provides L. lactis cells the means to ensure optimal CW plasticity without the need to control the expression of PG synthesis genes.
authors.affiliation: From the Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Solopova
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain, Croix du Sud 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium, and.
authors.forename: Cécile
authors.initials: C
authors.lastname: Formosa-Dague
authors.affiliation: Micalis Institute and.
authors.forename: Pascal
authors.initials: P
authors.lastname: Courtin
authors.affiliation: Micalis Institute and.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Furlan
authors.affiliation: Micalis Institute and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Veiga
authors.affiliation: Génétique Animale et Biologie Intégrative, Institut National de la Recherche Agronomique, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Péchoux
authors.affiliation: Micalis Institute and.
authors.forename: Julija
authors.initials: J
authors.lastname: Armalyte
authors.affiliation: Micalis Institute and.
authors.forename: Mikas
authors.initials: M
authors.lastname: Sadauskas
authors.affiliation: From the Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Kok
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain, Croix du Sud 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium, and.
authors.forename: Pascal
authors.initials: P
authors.lastname: Hols
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain, Croix du Sud 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium, and.
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
authors.affiliation: From the Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands.
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
authors.affiliation: Micalis Institute and.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chapot-Chartier
authors.affiliation: Micalis Institute and Saulius.Kulakauskas@jouy.inra.fr.
authors.forename: Saulius
authors.initials: S
authors.lastname: Kulakauskas
mesh_terms: D001221:Aspartate Carbamoyltransferase / Q000235:genetics / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism / Q000648:ultrastructure; D004548:Elasticity; D005798:Genes, Bacterial; D013294:Lactococcus lactis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D009113:Muramidase / Q000494:pharmacology; D009154:Mutation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D009711:Nucleotides; D010457:Peptidoglycan; D001224:Aspartic Acid; D001221:Aspartate Carbamoyltransferase; D009113:Muramidase; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: aspartate (aspartic acid); bacteria; cell wall; nucleoside/nucleotide metabolism; peptidoglycan