Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain.
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.
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Lisa
L
Kunsmann
Institute of Infectiology, Center for Molecular Biology of Inflammation (ZMBE), University of Münster, 48149 Münster, Germany.
Christian
C
Rüter
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Andreas
A
Bauwens
Institute of Infectiology, Center for Molecular Biology of Inflammation (ZMBE), University of Münster, 48149 Münster, Germany.
Lilo
L
Greune
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Malte
M
Glüder
Biomedical Technology Center, University of Muenster, 48149 Münster, Germany.
Björn
B
Kemper
National Reference Center for Salmonella and Other Enteric Pathogens, Robert Koch Institute, Branch Wernigerode, 38855 Wernigerode, Germany.
Angelika
A
Fruth
Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, S-90187 Umeå, Sweden.
Sun Nyunt
SN
Wai
Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture (USDA), Albany, CA 94710, USA.
Xiaohua
X
He
Laboratoire d'Ingenierie des Systemes Macromoleculaires UMR7255, CNRS-Aix-Marseille Université, 13402 Marseille cedex 20, France.
Roland
R
Lloubes
Institute of Infectiology, Center for Molecular Biology of Inflammation (ZMBE), University of Münster, 48149 Münster, Germany.
M Alexander
MA
Schmidt
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Ulrich
U
Dobrindt
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Alexander
A
Mellmann
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Helge
H
Karch
Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, 48149 Münster, Germany.
Martina
M
Bielaszewska
D001425:Bacterial Outer Membrane Proteins; D018938:Caco-2 Cells; D002478:Cells, Cultured; D004196:Disease Outbreaks; D004926:Escherichia coli / Q000145:classification* / Q000502:physiology*; D004927:Escherichia coli Infections / Q000382:microbiology*; D000067128:Extracellular Vesicles; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D022621:Shiga Toxin / Q000378:metabolism*; D013045:Species Specificity; D037521:Virulence Factors / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; C493898:Shiga toxin subunit A; D037521:Virulence Factors; D022621:Shiga Toxin