title: Characterization of outer membrane vesicles from a neonatal meningitic strain of Cronobacter sakazakii.
abstract: Cronobacter sakazakii is associated with severe and often fatal cases of infant meningitis and necrotizing enterocolitis. The form of meningitis differs from that due to Neisseria meningitidis and Streptococcus spp., in that it is highly invasive and destructive towards human brain cells. However, there is relatively little understanding of the cytopathogenic interaction of C. sakazakii with host cells which results in stimulation of an inflammatory immune response. The production of Cronobacter outer membrane vesicles (OMV) and their potential pathogenic functions have not yet been elucidated. This study is the first to show that C. sakazakii produce OMV, which may play a role in the activation of cytopathogenic and host cell responses on human intestinal epithelial cells. Cronobacter sakazakii strain 767 was used which had been isolated from a fatal outbreak of neonatal meningitis and necrotizing enterocolitis. Cronobacter sakazakii OMV were internalized by Caco-2 cells, increased cell proliferation and stimulated the host's innate proinflammatory response without inducing overt toxicity. A total of 18 OMV-associated proteins were identified by mass spectrometry and their potential pathogenicity roles were evaluated. Collectively, these data indicate that C. sakazakii OMV could play a role in pathogenesis by delivering bacterial toxins into host epithelial cells, driving proliferative and proinflammatory responses.
authors.affiliation: Pathogen Research Group, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
authors.forename: Hayat
authors.initials: H
authors.lastname: Alzahrani
authors.affiliation: Pathogen Research Group, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
authors.forename: Jody
authors.initials: J
authors.lastname: Winter
authors.affiliation: John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
authors.forename: David
authors.initials: D
authors.lastname: Boocock
authors.affiliation: Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.
authors.forename: Luigi
authors.initials: L
authors.lastname: De Girolamo
authors.affiliation: Pathogen Research Group, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK Stephen.forsythe@ntu.ac.uk.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forsythe
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism / Q000494:pharmacology*; D001427:Bacterial Toxins; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D044083:Cronobacter sakazakii / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000382:microbiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D016209:Interleukin-8
keywords: Cronobacter sakazakii; cytopathogenicity; meningitis; outer membrane vesicles; proteomic