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Vesicular stabilization and activity augmentation of enterohaemorrhagic Escherichia coli haemolysin.
Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Biology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
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2009 (English)In: Molecular microbiology, ISSN 1365-2958, Vol. 71, no 6, 1496-508 p.Article in journal (Refereed) Published
Abstract [en]
Haemolysin from enterohaemorrhagic Escherichia coli (EHEC-Hly), a putative EHEC virulence factor, belongs to the RTX (repeat-in-toxin) family whose members rapidly inactivate themselves by self-aggregation. By investigating the status of EHEC-Hly secreted extracellularly, we found the toxin both in a free, soluble form and associated, with high tendency and independently of its acylation status, to outer membrane vesicles (OMVs) extruded by EHEC. We compared the interaction of both toxin forms with erythrocytes using scanning electron microscopy and binding assays. The OMV-associated toxin was substantially (80 times) more stable under physiological conditions than the free EHEC-Hly as demonstrated by prolonged haemolytic activity (half-life time 20 h versus 15 min). The haemolysis was preceded by calcium-dependent binding of OMVs carrying EHEC-Hly to erythrocytes; this binding was mediated by EHEC-Hly. We demonstrate that EHEC-Hly is a biologically active cargo in OMVs with dual roles: a cell-binding protein and a haemolysin. These paired functions produce a biologically potent form of the OMV-associated RTX toxin and augment its potential towards target cells. Our findings provide a general concept for stabilization of RTX toxins and open new insights into the biology of these important virulence factors.
Place, publisher, year, edition, pages
2009. Vol. 71, no 6, 1496-508 p.
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Microbiology in the medical area
URN: urn:nbn:se:umu:diva-31624DOI: 10.1111/j.1365-2958.2009.06618.xPubMedID: 19210618OAI: diva2:293543
Available from: 2010-02-11 Created: 2010-02-11 Last updated: 2010-02-11

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Uhlin, Bernt EricWai, Sun Nyunt
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Molecular Biology (Faculty of Medicine)Molecular BiologyUmeå Centre for Microbial Research (UCMR)
Microbiology in the medical area

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