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.
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.
People |
ORCID iD |
| Stephanie Schuller (Primary Supervisor) | |
| Daniel Yara (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011216/1 | 01/10/2015 | 31/03/2024 | |||
| 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 (OMVs). 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. It has been found that certain gut cell models internalise OMVs and others do not. The reason for this is still not know. In addition, it has been found that the Shiga toxin (Stx) which is found within OMVs can also be internalised by certain cell types, where upon OMV internalisation, Stx is release and interacts with the golgi, followed by the endoplasmic reticulum. It has also been found that upon internalisation, OMVs interact with endosomes, which are then transported to the lysosome. The integrity of polarised monolayers are not affects by OMV exposure, where it has been found that OMVs cross this cellular barrier. |
| 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 |