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Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain

Lisa Kunsmann, Christian Rüter, Andreas Bauwens, Lilo Greune, Malte Glüder, Björn Kemper, Angelika Fruth, Sun Nyunt Wai, Xiaohua He, Roland Lloubes, M. Alexander Schmidt, Ulrich Dobrindt, Alexander Mellmann, Helge Karch, Martina Bielaszewska
Scientific Reports 2015 v.5 no.article 13252 pp. -
Escherichia coli, Shiga toxin, Shigella, apoptosis, cytotoxicity, diarrhea, endocytosis, enterotoxins, flagellin, humans, interleukin-8, intestinal mucosa, lipopolysaccharides, secretion, virulence
The highly virulent Escherichia coli O104:H4 that caused the large 2011 outbreak of diarrhoea and haemolytic uraemic syndrome secretes blended virulence factors of enterohaemorrhagic and enteroaggregative E. coli, but their secretion pathways are unknown. We demonstrate that the outbreak strain releases a cocktail of virulence factors via outer membrane vesicles (OMVs) shed during growth. The OMVs contain Shiga toxin (Stx) 2a, the major virulence factor of the strain, Shigella enterotoxin 1, H4 flagellin, and O104 lipopolysaccharide. The OMVs bind to and are internalised by human intestinal epithelial cells via dynamin-dependent and Stx2a-independent endocytosis, deliver the OMV-associated virulence factors intracellularly and induce caspase-9-mediated apoptosis and interleukin-8 secretion. Stx2a is the key OMV component responsible for the cytotoxicity, whereas flagellin and lipopolysaccharide are the major interleukin-8 inducers. The OMVs represent novel ways for the E. coli O104:H4 outbreak strain to deliver pathogenic cargoes and injure host cells.