How to build a biofilm
Lead Research Organisation:
University of Dundee
Department Name: College of Life Sciences
Abstract
A house is made from basic components that include bricks, roof tiles and mortar. Each part is essential to allow the building to be constructed. In addition the component parts need to be assembled in the correct order, and with the correct spatial arrangement, for the house to be strong and secure. Following this analogy, biofilms are communities of microbes (where the cells can be considered the bricks and roof tiles) that are surrounded by an extracellular matrix (the mortar) that provides structure. When living in the biofilm the microbes benefit and become resistant to antibiotics and other antimicrobial agents. This can result in the formation of chronic antibiotic resistant infections. We are interested in how a biofilm is built. The main component parts that are needed have been identified and in this proposal we aim to understand how they are assembled. Understanding how they are assembled will allow the development of novel strategies to block assembly in the natural environment and therefore guide future development of novel antimicrobial compounds for chronic debilitating biofilm infections.
Technical Summary
It is accepted across the medical and scientific community that there is an urgent need to uncover new targets to fight difficult-to-treat Gram-positive and Gram-negative chronic bacterial infections. Such infections are predominantly the result of microbial biofilms; structured complex communities of microbial cells that are enclosed in a self-produced extracellular matrix. There have been significant recent advances in our understanding of the regulatory pathways and key building blocks required for the nucleation and growth of biofilms for many species of bacteria. However it is still not understood how the extracellular and cell wall components physically interact to allow a three dimensional biofilm to develop. Bacillus subtilis is a very suitable model for biofilm formation in Gram-positive bacteria. It forms biofilms that contain differentiated cells that display a complex three-dimensional architecture. We have recently shown that a small protein called YuaB is essential for biofilm formation and that it acts in a synergistic manner with the TasA amyloid fibres and the exopolysaccharide found in the extracellular matrix to allow biofilm development. Therefore our system is ideally suited to allow us to generate a detailed understanding of how the biofilm is constructed. We aim to determine when YuaB is needed to allow biofilm formation, how the extracellular polymers interact with each other, and to elucidate the structure and function of YuaB. We will accomplish this using a collaborative interdisciplinary approach with techniques that cross the boundaries of biology and chemistry. We will utilise a combination of classical molecular genetic techniques, in association with state-of-the-art chemical and structural analyses.
Planned Impact
A. i) Smaller Biotech companies such as Novacta, Biotica, and Aquapharm. ii) These companies have active anti-infective research programmes. They will benefit from the proposed research programme that will generate novel and exciting knowledge on a target relevant to the development of novel antibiofilm agents. iii) It is currently too early in the project to identify industrial partners specifically. The lead institution will act to protect any intellectual property and to maximise opportunities for collaborative research or licensing. The Dundee research and innovation team have a wealth of industrial contacts and close links to Scottish Enterprise, and will help maximise the impact of all findings of commercial value. As and when appropriate, results will be peer-reviewed and published. B. i) Members of the wider academic community. ii) Biofilms are responsible for the majority of chronic infections and also the majority of beneficial remediation and biocontrol processes. This work will increase our understanding of the role and mechanisms of the extracellular matrix of the biofilm thus facilitating future study and exploitation for therapeutic purposes. iii) The PDRA and PIs will attend and contribute to a variety of conferences and the PIs will present results through invited research talks, both nationally and internationally. As appropriate, results will be peer-reviewed and published. Strains and other resources will be made available as appropriate. C. i) PDRA and PIs. ii) The University of Dundee takes training of early career researchers (including PIs) very seriously, thereby ensuring a successful contribution to the knowledge-led economy of UK Plc. The appointed PDRA will be encouraged to be innovative in their work. There will be opportunities for them to train undergraduate, postgraduate and visiting scientists. They will be given multiple opportunities to present their findings at major research conferences, facilitating their career development through the acquisition and refining of key presentational and networking skills. iii) The appointed PDRA will have access to training in transferable/generic skills through the professional development schemes. In line with the Concordat 2009, the PDRA will be actively encouraged to undertake at least 5 days training in generic skills per annum. In addition, both institutes have an annual appraisal scheme to actively facilitate the career development of staff, including PDRAs and PIs. The PDRA will also be encouraged to design and supervise undergraduate projects and to become involved in science communication. D. i) The general public. ii) It is important that members of the general public are aware and supportive of how tax payers' money is spent on scientific research. Therefore as part of our work on this project, we will engage with local communities, through face-to-face discussion of our work and family focussed scientific event days. iii) The applicants are experienced, energetic and ardent science communicators. For example, the University of Dundee partners have teamed up with the Dundee Science Centre to organize a 2-day event in May 2010 entitled 'Magnificent Microbes'. This event attracted teachers, children, the general public and the local media to learn about the research going on in the Division of Molecular Microbiology and educated, inspired and entertained the public about microbiology research. Approximately 400 people visited the event and we now intend to repeat it in 2012, which would be during the course of the project.
Publications
Marlow VL
(2013)
Blast a biofilm: a hands-on activity for school children and members of the public.
in Journal of microbiology & biology education
Hobley L
(2013)
BslA is a self-assembling bacterial hydrophobin that coats the Bacillus subtilis biofilm.
in Proceedings of the National Academy of Sciences of the United States of America
Hobley L
(2014)
Norspermidine is not a self-produced trigger for biofilm disassembly.
in Cell
Gerwig J
(2014)
The protein tyrosine kinases EpsB and PtkA differentially affect biofilm formation in Bacillus subtilis.
in Microbiology (Reading, England)
Gillespie RM
(2014)
Enzymes in action: an interactive activity designed to highlight positive attributes of extracellular enzymes synthesized by microbes.
in Journal of microbiology & biology education
Marlow VL
(2014)
Phosphorylated DegU manipulates cell fate differentiation in the Bacillus subtilis biofilm.
in Journal of bacteriology
Cairns LS
(2014)
Biofilm formation by Bacillus subtilis: new insights into regulatory strategies and assembly mechanisms.
in Molecular microbiology
Hobley L
(2015)
Giving structure to the biofilm matrix: an overview of individual strategies and emerging common themes.
in FEMS microbiology reviews
Stanley-Wall NR
(2015)
Connecting the dots between bacterial biofilms and ice cream.
in Physical biology
Cairns LS
(2015)
An alternate route to phosphorylating DegU of Bacillus subtilis using acetyl phosphate.
in BMC microbiology
Title | Animation - raincoat |
Description | Animation about scientific research |
Type Of Art | Film/Video/Animation |
Year Produced | 2015 |
Impact | Been used widely for both scientific and public presentations. Has been widely viewed by members of the public. Has been used in art exhibitions. |
URL | https://www.youtube.com/watch?v=TME-V7D2saY |
Description | The majority of bacteria are capable of protecting themselves by making a community or structure that is called a biofilm. It contained many millions of cells that are embedded in a self-produced stick matrix. We were interested in how the biofilm is built. We wanted to know what materials the bacteria used to build the community and also how these materials functioned. We uncovered that a common bacterium found in the soil, called Bacillus subtilis, uses a protein called BslA not only to allow the bacteria to structure their local environment but also to make it hydrophobic. This means that water and other liquids cannot easily get inside. The bacteria are effectively making a raincoat to protect the residents. What was particularly exciting was that we solved the crystal structure of BslA, which let us learn how the protein works in exquisite detail. The way the protein works is really novel. We also found out that the protein has a lot of uses in biotechnology and therefore we explored how it might work to stabilise formulations. This became the focus of future work that was funded to explore commercial development of the protein. |
Exploitation Route | Working out how BslA works at the protein level turned out to be very important. The impact was felt not only in the area of biofilm formation but also in industrial sectors. We have seen multiple industries express an interest in using BslA in their formulations. This means that potentially there could be new or improved products generated. |
Sectors | Agriculture Food and Drink Chemicals Education Manufacturing including Industrial Biotechology |
Description | The finding that the protein made by Bacillus subtilis, called BslA, has industrial uses led us to protect the innovation through a patent application. The patent has been published and has stimulated industrial interest in the application of BslA. The fact that the bacteria form an obviously hydrophobic layer has also been an excellent tool to talk with members of the public about how and why bacteria living in biofilms can become tolerant to antibiotics. Seeing water droplets sitting on top of the cells is a very visual way to explain the protective mechanisms that are employed by bacteria in biofilms to ensure their survival. |
First Year Of Impact | 2011 |
Sector | Education,Manufacturing, including Industrial Biotechology |
Impact Types | Cultural Economic |
Description | Vacation Scholarship 2010 |
Amount | £1,880 (GBP) |
Organisation | Society of General Microbiology |
Sector | Charity/Non Profit |
Country | European Union (EU) |
Start | 05/2010 |
End | 08/2010 |
Description | Biophysics |
Organisation | University of Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We contribute biological knowledge and expertise. This included intellectual input and also training for staff. |
Collaborator Contribution | Partner contributes biophysical knowledge and expertise. This included intellectual input and also training for staff. |
Impact | PMID: 26685107 PMID: 26378478 PMID: 25907113 PMID: 25870300 PMID: 23904481 |
Start Year | 2012 |
Description | Continued professional development Primary School Teachers |
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 | Primary school CPD on the topic of microbiology. Raising awareness of experiments that can be done with microbes and increasing confidence. |
Year(s) Of Engagement Activity | 2016 |
Description | Dundee Science Centre International Women's Day Campaign |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | The goal was to capture stories of female role models who inspired people in STEM to get into their respective fields. The role models do not necessarily need to have an obvious STEM background; it may be a family member, a teacher, a coach or anyone else. The stories provided were shared with Dundee Science Centre (DSC). The content will be a part of their campaign during International Women's Day w/c 7th March. DSC will promote some of these stories on their website, social media platforms, and in their reception area throughout March so that visitors can also be inspired. The University of Dundee will also use the materials for similar purposes. |
Year(s) Of Engagement Activity | 2022 |
URL | https://discovery.dundee.ac.uk/en/activities/dundee-science-centre-international-womens-day-campaign |
Description | Magnificent Microbes 2014 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Outreach event Dundee Science Centre March 2014. Two days - one for school children and the other for members of the public. "Magnificent Microbes" is organised and run by Dr. Nicola Stanley-Wall. The activity involves many members of the division of Molecular Microbiology from technical staff, PhD students, postdoctoral scientists to academic staff. Magnificent Microbes is an innovative outreach event designed to educate, inspire and entertain large numbers of school children and family groups about microbes, the roles that they play in shaping our environment, and how they influence the food, health, and green energy sectors of our economy. The activity involved many members of the division of Molecular Microbiology from technical staff, PhD students,postdoctoral scientists to academic staff. Teachers reported increased confidence to undertake microbiology related activities in the classroom. |
Year(s) Of Engagement Activity | 2013,2014 |
URL | http://blog.wellcome.ac.uk/2014/06/05/how-to-get-researchers-involved-in-public-engagement/ |
Description | Magnificent Microbes 2022 |
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 | Final year (P7) primary school pupils from Forthill Primary and Dens Road Primary participated in Magnificent Microbes. Participating classes received a full week's worth of fun and hands-on science activities centred around the world of microbes, complete with a box full of materials and lots of chances to interact with our scientists through video and text chats. An overview of the week's activities is as follows: Magnificent Microbes week began with a video introducing some of our microbiologists at various stages of their careers, from undergraduate to professor and in between! They shared facts about microbes as well as information about their research, and then challenged pupils to explore the world of microbes using the resources provided. Classes were invited to begin creating their own special microbes using crafting supplies and write a class poem about the science they learned. Tuesday introduced pupils to microbe record breakers - microbes hardy enough to live in deep sea vents, arctic caves, and even outer space! Scientists ran a video quiz for classes to help them learn all about these amazing adaptations. On Wednesday pupils learned about bacterial warfare and cooperation. Starting with a fun animation that explains how microbes fight and cooperate within their environment, the lesson challenged the pupils to become microbes themselves and to talk to the other pupils to find out their perfect pair through our cooperation game. They also worked on their microbe creations, adding in details about how they interact with other microbes, whether friendly or not On Thursday the lessons covered the interactions between microbes and plants, which are more complex than you might expect! Pupils had a chance to look through microscopes at a variety of bacterial samples as well as playing a 'happy microbe families' game to build a healthy microbiome. Friday started with activities around Antimicrobial Resistance, or AMR, a big problem facing scientists and doctors today. Pupils learned about antibiotics - their history, where they come from, and how they work - before finding out about how bacteria have evolved to fight back against them. The classes had the chance to make microbial prints on real agar plates that were collected and incubated back at our labs. At the end of the week we held an interactive Q&A video chat for all classes so they could speak to our scientists and ask them about Magnificent Microbes! It was a very lively session full of lots of interesting questions and answers. |
Year(s) Of Engagement Activity | 2022 |
URL | https://discovery.dundee.ac.uk/en/activities/magnificent-microbes-2022 |
Description | Microbiology Lessons in the classroom |
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 | Input to primary school microbiology lessons provided for a year group. Provided printed materials and physical resources to the teacher including agar plates, microscope and books. Also provided support to teacher in enhancing knowledge of content. |
Year(s) Of Engagement Activity | 2022 |
URL | https://discovery.dundee.ac.uk/en/activities/microbiology-lessons-in-the-classroom |
Description | Outreach event (London) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | talking with members of the public sparked interest and curiosoty in BBSRC funded research After the event approx 7000 people had been engaged and stimulated by British bioscience. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.bbsrc.ac.uk/engagement/exhibitions/gb-bioscience-festival/ |
Description | Plant Science (Tayport) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | We initiated a citizen science project with a local community garden organisation. We had multiple interactions with the volunteers at PLANT and we also ran two events where members of the public were encouraged to bring soil and isolate spore forming bacteria called Bacillus subtilis. We have used these strains in our research. |
Year(s) Of Engagement Activity | 2017 |
Description | Talk- John Innes Centre |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Talk invited outreach and research Talk at IFR outreach event organised by PhD students. The goal was to spark interest in outreach activities and get scientists thinking about what is possible. The views of the scientists were positively impacted by the event. Contacted by school teacher for help with in school activities. |
Year(s) Of Engagement Activity | 2013 |
Description | continuted professioal development (teachers) |
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 | Talks sparked interest and discussions The teachers have gained confidence and have increased the partical activities they undertake in the classroom in topic relating to microbiology |
Year(s) Of Engagement Activity | 2015 |
Description | media interest (uses of novel biologic) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | We released a press statment about on going work with the goal of stimulating business interest The work was covered by many media outlets and also several small adn multinational businesses have made contact and we are currently in disucssions with them. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.dundee.ac.uk/news/2015/slower-melting-ice-cream-in-pipeline-thanks-to-new-ingredient.php |
Description | schools visit (Dundee) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | talks sparked thinking about how science is reported in the media Children reported thinking about the "headlines" in newspaers and online media in different ways. School gained confience to enter a competition. |
Year(s) Of Engagement Activity | 2015 |
Description | schools visit (carnoustie) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | talk sparked interest and many many questions from the children. After the event the children in the class undertook further experiments and reported the findings back to us. |
Year(s) Of Engagement Activity | 2015 |