Bacterial bombs or stress response - how does the environment influence production and function of bacterial outer membrane vesicles?

Lead Research Organisation: University of East Anglia
Department Name: Graduate Office

Abstract

Outer membrane vesicles (OMVs) are naturally secreted by Gram-negative bacteria by bulging of the outer membrane and selective packaging of bacterial molecules within spherical vesicles. OMVs are part of the bacterial stress response and necessary for bacterial detoxification and survival. In addition, many other functions such as biofilm formation, antimicrobial activity, nutrient acquisition, and delivery of biomolecules, have been described. Due to their immunogenic properties, OMVs are also increasingly used in vaccine development. Despite these advances, little is known about OMV biogenesis and the factors determining OMV formation, their molecular composition, and interaction with host cells.
In this project, we will investigate OMV production by the foodborne pathogen enterohaemorrhagic E. coli (EHEC) which naturally resides in the intestinal tract of cattle. It also persists in the environment for prolonged periods of time, predominantly within protozoa. In humans, EHEC colonises the colon and is a major cause of diarrhoea worldwide. It can also lead to haemolytic uraemic syndrome, a severe systemic complication affecting the kidneys and central nervous system.
The aim of this study is to determine the effect of environmental conditions relevant to the different habitats of EHEC (cattle, humans, external environment) on OMV production and function with particular focus on OMV release, protein composition, and interaction with host cells.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 30/09/2023
1805613 Studentship BB/M011216/1 01/10/2016 30/09/2020 Daniel Yara
 
Description That under certain conditions found in the gut, pathogenic E. coli increases its production of vesicles. Such vesicles have been found to contain shiga toxin which can lead to disease. Hence, coupled with this data, it may provide a reason on how disease develops upon infection.
Exploitation Route By understanding how disease develops, this can provide a different route on how to tackle the infection. Also vesicles have been used in vaccines therefore vaccination against this infection may be developed in the future.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Luis Ángel Fernández, nanobodies 
Organisation Spanish National Research Council (CSIC)
Department National Center for Biotechnology (CNB)
Country Spain 
Sector Public 
PI Contribution In vitro organ culture studies where made to evaluate whether EHEC-specific nanobodies which were constructed and synthesised by Fernandez et al, inhibited the ability of EHEC to colonise the colon. Here I found that EHEC colonisation did decrease upon expose to these nanobodies, which were assessed by immuno-fluorescently labelling EHEC (attached to the colonic biopsies).
Collaborator Contribution Design, synthesis and biochemical experiments had been carried out with the nanobodies. Further work was needed to carry out biological test, hence I was involved to assess the ability of these nanobodies to inhibit EHEC colonisation.
Impact It is anticipated a scientific academic paper will be produce.
Start Year 2018
 
Description My first day as a Microbiologist! Norwich Science Festival- The Forum 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A make-shift lab was made in the public space so the people may experience what life in a lab is like. I was participated in demonstrating the microscope and the hand-wash challenge. I prepared samples from yoghurts and showed people (general public) what microbes were present in such items. I them explained that it was important to have good bacteria in the gut as they could be involved in health.
In the hand washing challenge, glitter gel was used to represent microbes. Here, I showed the importance of washing hands and that disease can spread by not washing hands properly.
Many questions arose and in general I believe interest was sparked.
Year(s) Of Engagement Activity 2017