Title |
Interaction of Bacteroides fragilis Toxin with Outer Membrane Vesicles Reveals New Mechanism of Its Secretion and Delivery
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Published in |
Frontiers in Cellular and Infection Microbiology, January 2017
|
DOI | 10.3389/fcimb.2017.00002 |
Pubmed ID | |
Authors |
Natalya B. Zakharzhevskaya, Vladimir B. Tsvetkov, Anna A. Vanyushkina, Anna M. Varizhuk, Daria V. Rakitina, Victor V. Podgorsky, Innokentii E. Vishnyakov, Daria D. Kharlampieva, Valentin A. Manuvera, Fedor V. Lisitsyn, Elena A. Gushina, Vassili N. Lazarev, Vadim M. Govorun |
Abstract |
The only recognized virulence factor of enterotoxigenic Bacteroides fragilis (ETBF) that accompanies bloodstream infections is the zinc-dependent non-lethal metalloprotease B. fragilis toxin (BFT). The isolated toxin stimulates intestinal secretion, resulting in epithelial damage and necrosis. Numerous publications have focused on the interrelation of BFT with intestinal inflammation and colorectal neoplasia, but nothing is known about the mechanism of its secretion and delivery to host cells. However, recent studies of gram-negative bacteria have shown that outer membrane vesicles (OMVs) could be an essential mechanism for the spread of a large number of virulence factors. Here, we show for the first time that BFT is not a freely secreted protease but is associated with OMVs. Our findings indicate that only outer surface-exposed BFT causes epithelial cell contact disruption. According to our in silico models confirmed by Trp quenching assay and NMR, BFT has special interactions with outer membrane components such as phospholipids and is secreted during vesicle formation. Moreover, the strong cooperation of BFT with polysaccharides is similar to the behavior of lectins. Understanding the molecular mechanisms of BFT secretion provides new perspectives for investigating intestinal inflammation pathogenesis and its prevention. |
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United States | 3 | 30% |
France | 2 | 20% |
Switzerland | 1 | 10% |
Chile | 1 | 10% |
Canada | 1 | 10% |
Unknown | 2 | 20% |
Demographic breakdown
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Scientists | 3 | 30% |
Mendeley readers
Geographical breakdown
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Unknown | 67 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 15 | 22% |
Researcher | 11 | 16% |
Student > Bachelor | 10 | 15% |
Student > Doctoral Student | 3 | 4% |
Student > Postgraduate | 3 | 4% |
Other | 8 | 12% |
Unknown | 17 | 25% |
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Agricultural and Biological Sciences | 9 | 13% |
Immunology and Microbiology | 6 | 9% |
Medicine and Dentistry | 2 | 3% |
Chemistry | 2 | 3% |
Other | 4 | 6% |
Unknown | 20 | 30% |