title: Group B streptococcal beta-hemolysin/cytolysin promotes invasion of human lung epithelial cells and the release of interleukin-8.
abstract: Pneumonia and lung injury are hallmarks of early-onset neonatal group B streptococcal (GBS) infections. Production of a beta-hemolysin/cytolysin (beta-h/c) encoded by the cylE gene is associated with GBS virulence in vivo. To elucidate the contribution of the beta-h/c toxin to lung injury, the interactions of GBS wild-type strains and isogenic cylE mutants with A549 lung epithelial cells were examined. Compared with wild-type GBS strains, cylE mutants did not produce cytolytic injury, even at high inocula, and exhibited decreased cellular invasion. Additionally, cylE mutants induced less A549 cell release of the neutrophil chemoattractant interleukin (IL)-8. GBS invasion and IL-8 induction were significantly reduced in the presence of dipalmotyl phosphatidylcholine, a major constituent of lung surfactant and a known inhibitor of beta-h/c activity. These data indicate that the GBS beta-h/c contributes to invasion and immune activation of lung epithelial cells and may represent a multifunctional virulence factor in the early pulmonary stages of GBS infection.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Doran
authors.forename: Jennifer C W
authors.initials: JC
authors.lastname: Chang
authors.forename: Vivian M
authors.initials: VM
authors.lastname: Benoit
authors.forename: Lars
authors.initials: L
authors.lastname: Eckmann
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D001422:Bacterial Adhesion; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D006460:Hemolysin Proteins / Q000032:analysis / Q000633:toxicity*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000472:pathogenicity*
chemical_list: D006460:Hemolysin Proteins; D016209:Interleukin-8; D015060:1,2-Dipalmitoylphosphatidylcholine