title: Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes.
abstract: The dlt operon of Gram-positive bacteria comprises four genes (dltA, dltB, dltC and dltD) that catalyse the incorporation of D-alanine residues into the cell wall-associated lipoteichoic acids (LTAs). In this work, we characterized the dlt operon of Listeria monocytogenes and constructed a D-Ala-deficient LTA mutant by inactivating the first gene (dltA) of this operon. The DltA- mutant did not show any morphological alterations and its growth rate was similar to that of the wild-type strain. However, it exhibited an increased susceptibility to the cationic peptides colistin, nisin and polymyxin B. The virulence of the DltA- mutant was severely impaired in a mouse infection model (4 log increase in the LD50) and, in vitro, the adherence of the mutant to various cell lines (murine bone marrow-derived macrophages and hepatocytes and a human epithelial cell line) was strongly restricted, although the amounts of surface proteins implicated in virulence (ActA, InlA and InlB) remains unaffected. We suggest that the decreased adherence of the DltA- mutant to non-phagocytic and phagocytic cells might be as a result of the increased electronegativity of its charge surface and/or the presence at the bacterial surface of adhesins possessing altered binding activities. These results show that the D-alanylation of the LTAs contributes to the virulence of the intracellular pathogen L. monocytogenes.
authors.affiliation: Laboratoire de Microbiologie, INSERM U-411, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Abachin
authors.forename: Claire
authors.initials: C
authors.lastname: Poyart
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pellegrini
authors.forename: Eliane
authors.initials: E
authors.lastname: Milohanic
authors.forename: Franz
authors.initials: F
authors.lastname: Fiedler
authors.forename: Patrick
authors.initials: P
authors.lastname: Berche
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
mesh_terms: D000409:Alanine / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins; D001483:Base Sequence; D018938:Caco-2 Cells; D004269:DNA, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D007424:Intracellular Fluid / Q000382:microbiology; D008070:Lipopolysaccharides / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009876:Operon; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013682:Teichoic Acids / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C026244:alanyl-lipoteichoic acid; C009900:lipoteichoic acid; C408973:DltD protein, bacteria; D013869:Thiolester Hydrolases; D000409:Alanine