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Can bacterial outer membrane vesicles drive haemorrhagic diseases?

 

PI: Waltraud Schrottmaier
Co-PI with Prof. Bernd Jilma (MUW)
Funded by: Medical Scientific Fund of the Mayor of the City of Vienna (BGM19029)
Funding period: 06/2019-09/2020

Cholera disease, caused by infection with the bacterium Vibrio cholerae, is a gastro-intestinal disease characterized by severe diarrhoea. Annually more than 2.8 million people worldwide are affected by cholera. Via shedding of outer membrane vesicles (OMV), V. cholerae is able to neutralize factors of the immune responses such as the complement system or antimicrobial proteins, enabling the pathogen to evade host immune defences. Furthermore, cholera infection may also lead to serious complications such as intestinal haemorrhages which drastically increase mortality.

As cellular mediators of haemostasis, platelets are of pivotal importance for maintaining vascular integrity by adhering to the damaged endothelium and sealing breaches of the vessel. Furthermore, platelets also respond to immune stimuli including bacterial infection. Thus, platelet dysfunction is generally associated with increased risk for bleeding and may be directly influenced by pathogens.

Although platelets play a central role in several haemorrhagic pathologies, there is currently little data available on how platelet-mediated primary haemostasis is affected by V. cholerae or their OMVs. Further the mechanisms underlying haemorrhagic complications during cholera infection remain unknown. Hence, we aim to elucidate how V. cholerae-derived OMVs modulate platelet activation.

Based on our preliminary data, we think that OMVs shed from V. cholera influence platelet function and regulate their capacity to form thrombi, which could lead to altered vascular integrity and may reflect haemostatic complications suffered by some V. cholera-infected patients.

Thus, we are investigating the effect of V. cholerae-derived OMVs on platelet activation in vitro. Further, we aim to identify the pathogenic factors involved in platelet-OMV interaction and their effect on platelet function. 

VPL - Vienna Platelet Laboratories
Schwarzspanierstrasse 17
1090 Wien

Tel.: +43 1 40160 31405

Mail: alice.assinger@meduniwien.ac.at

 

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