title: Components of the peptidoglycan-recycling pathway modulate invasion and intracellular survival of Salmonella enterica serovar Typhimurium.
abstract: beta-Lactam resistance in enteric bacteria is frequently caused by mutations in ampD encoding a cytosolic N-acetylmuramyl- l-alanine amidase. Such mutants are blocked in murein (peptidoglycan) recycling and accumulate cytoplasmic muropeptides that interact with the transcriptional activator ampR, which de-represses beta-lactamase expression. Salmonella enterica serovar Typhimurium, an extensively studied enteric pathogen, was used to show that mutations in ampD decreased the ability of S. typhimurium to enter a macrophage derived cell line and made the bacteria more potent as inducers of inducible nitric oxide synthase (iNOS), as compared with the wild-type. ampG mutants, defective in the transport of recycled muropeptides across the cytoplasmic membrane, behaved essentially as the wild-type in invasion assays and in activation of iNOS. As ampD mutants also have reduced in vivo fitness in a murine model, we suggest that the cytoplasmic accumulation of muropeptides affects the virulence of the ampD mutants.
authors.affiliation: Mikrobiologiskt och Tumörbiologiskt Centrum, Karolinska Institutet, S-17177 Stockholm, Sverige, Sweden. Anders.Folkesson@biocentrum.dtu.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Folkesson
authors.forename: Sofia
authors.initials: S
authors.lastname: Eriksson
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.forename: James T
authors.initials: JT
authors.lastname: Park
authors.forename: Staffan
authors.initials: S
authors.lastname: Normark
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000032:analysis; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D008264:Macrophages / Q000382:microbiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D010457:Peptidoglycan / Q000378:metabolism*; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000502:physiology*; D013154:Spleen / Q000382:microbiology; D014774:Virulence
chemical_list: C089745:1,6-anhydro N-acetylmuramyl-alanyl-glutamyl-diaminopimelic acid; C084284:AmpG protein, Bacteria; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D010457:Peptidoglycan; D009569:Nitric Oxide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C062460:AmpD protein, Bacteria; D009238:N-Acetylmuramoyl-L-alanine Amidase