title: Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells.
abstract: D-alanylation of lipoteichoic acid (LTA), allows Gram-positive bacteria to modulate their surface charge, regulate ligand binding and control the electromechanical properties of the cell wall. In this study, the role of D-alanyl LTA in the virulence of the extracellular pathogen Streptococcus agalactiae was investigated. We demonstrate that a DltA- isogenic mutant displays an increased susceptibility to host defence peptides such as human defensins and animal-derived cationic peptides. Accordingly, the mutant strain is more susceptible to killing by mice bone marrow-derived macrophages and human neutrophils than the wild-type strain. In addition, the virulence of the DltA- mutant is severely impaired in mouse and neonatal rat models. This mutant was eliminated more rapidly than the wild-type strain from the lung of three-week-old mice inoculated intranasally and, consequently, is unable to induce a pneumonia. Finally, after intravenous injection of three-week-old mice, the survival of the DltA- mutant is markedly reduced in the blood in comparison to that of the wild-type strain. We hypothesize that the decreased virulence of the DltA- mutant is a consequence of its increased susceptibility to cationic antimicrobial peptides and to killing by phagocytes. These results demonstrate that the D-alanylation of LTA contributes to the virulence of S. agalactiae.
authors.affiliation: Laboratoire Mixte Pasteur-Necker de Recherche sur les Streptocoques et Streptococcies, Faculté de Médecine Necker-Enfants Malades, 75730 Paris Cedex 15, France. poyart@necker.fr
authors.forename: Claire
authors.initials: C
authors.lastname: Poyart
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pellegrini
authors.forename: Michael
authors.initials: M
authors.lastname: Marceau
authors.forename: Marina
authors.initials: M
authors.lastname: Baptista
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Lamy
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000382:microbiology; D001422:Bacterial Adhesion / Q000235:genetics; D001770:Blood Bactericidal Activity; D001921:Brain / Q000382:microbiology / Q000473:pathology; D023082:Defensins / Q000494:pharmacology*; D004847:Epithelial Cells; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000382:microbiology; D010587:Phagocytosis; D051381:Rats; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013292:Streptococcus agalactiae / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D023082:Defensins; D013682:Teichoic Acids; C026244:alanyl-lipoteichoic acid