|KUNSMANN, LISA - University Of Munster|
|RUTER, CHRISTIAN - University Of Munster|
|BAUWENS, ANDREAS - University Of Munster|
|GREUNE, LILO - University Of Munster|
|GLUDER, MALTE - University Of Munster|
|KEMPER, BJORN - University Of Munster|
|FRUTH, ANGELIKA - Robert Koch Institute|
|WAI, SUN NYUNT - University Of Umea|
|LLOUBES, ROLAND - Aix-Marseille University|
|SCHMIDT, ALEXANDER - University Of Munster|
|DOBRINDT, ULRICH - University Of Munster|
|MELLMANN, ALEXANDER - University Of Munster|
|KARCH, HELGE - University Of Munster|
|BIELASZEWSKA, MARTINA - University Of Munster|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/22/2015
Publication Date: 8/18/2015
Publication URL: http://handle.nal.usda.gov/10113/61409
Citation: Kunsmann, L., Ruter, C., Bauwens, A., Greune, L., Gluder, M., Kemper, B., Fruth, A., Wai, S., He, X., Lloubes, R., Schmidt, A.M., Dobrindt, U., Mellmann, A., Karch, H., Bielaszewska, M. 2015. Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Scientific Reports. doi: 10.1038/srep13252.
Interpretive Summary: Escherichia coli O104:H4, which caused a massive outbreak in 2011 with nearly 4000 infected persons, more than 900 cases of haemolytic uraemic syndrome (HUS) and 54 deaths, is a hybrid of enterohaemorrhagic (EHEC) and enteroaggregative (EAEC) E. coli. The strain harbors virulence genes from both of these E. coli. The mechanism of how the outbreak strain secretes its virulence factors is presently unknown. This research identified and characterized outer membrance vesicles (OMVs) from the E. coli O104:H4 outbreak strain and demonstrated that the bacterial strain released virulence factors via OMVs, which in turn are internalized by human intestinal cells and thereby delivered the virulence factors directly into the target cells, causing cell injury and inflammatory responses. This study also suggests that OMVs may be used as potential vaccine candidates to prevent disease caused by E. coli O104:H4.
Technical Abstract: 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.