Studies of nutrient uptake in Mycobacterium bovis - the causative agent of bovine tuberculosis
Lead Research Organisation:
University of Warwick
Department Name: School of Life Sciences
Abstract
Bovine tuberculosis is a disease of global importance. It is estimated that the worldwide losses to agriculture from this disease amount to $3 billion per annum. The major causative agent of bovine tuberculosis (TB) is Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex. Bovine TB is a disease of high economic relevance within livestock farming since it directly affects animal productivity and influences the export of meat and dairy products.
In this project we want to determine how M. bovis obtains and exploits essential nutrients - with the aim of determining the essentiality of these uptake systems and determining the structure, function and mechanisms of these transport systems. We will undertake a cutting-edge multidisciplinary approach to understand the key nutrient transport processes of this pathogen. This research has clear potential to impact on the agricultural industry with biotechnological applications.
In this project we want to determine how M. bovis obtains and exploits essential nutrients - with the aim of determining the essentiality of these uptake systems and determining the structure, function and mechanisms of these transport systems. We will undertake a cutting-edge multidisciplinary approach to understand the key nutrient transport processes of this pathogen. This research has clear potential to impact on the agricultural industry with biotechnological applications.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M01116X/1 | 01/10/2015 | 31/03/2024 | |||
| 1642867 | Studentship | BB/M01116X/1 | 05/10/2015 | 02/07/2020 | Magdalena Karlikowska |
| Description | Bovine tuberculosis (bTB) is one of the biggest challenges currently facing cattle farmers in the UK. The major causative agent of bovine TB is Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTBC). M. bovis is genetically identical to the most important bacterial pathogen of humans from the MTBC is M. tuberculosis (Mtb) - the causative agent of tuberculosis (TB) which remains one of the most difficult infectious diseases to control in the world. Mtb possesses a low number of carbohydrate transporters: four ATP-binding cassette (ABC) importers and one major facilitator superfamily permease, potentially reflecting the poor nutrient availability inside the host. This study aimed to elucidate the physiological function of three of these putative sugar transporters (UspABC, UgpABCE and SugI) and a sugar metabolism enzyme (NagA) in the model organism Mycobacterium smegmatis and the human pathogen Mtb. M. smegmatis was used as the host strain for characterisation of Mtb_uspC and Mtb_uspABC. Furthermore, gene knockout mutants were generated in M. smegmatis for the uspC, uspABC and nagA genes and in Mtb for the nagA, sugI and ugpABCE genes. The mutant strains were subjected to phenotypic (via Biolog microarrays), transcriptomic (via RNA-sequencing) and proteomic (via mass spectrometry) analyses to elucidate global quantitative differences between each mutant and the wild type strains. Taken together, the findings presented here provide novel insights into the physiological role of nutrient acquisition by Mtb. This knowledge of nutrient import has the potential to inform future bTB and TB diagnostics and treatment. |
| Exploitation Route | This PhD has provided knowledge required to formulate novel hypotheses and opened up new avenues for further research. The multi-omics approach provided a comprehensive and global picture of biological processes related to the putative sugar transporters and metabolism enzyme leading to a better understanding of mycobacterial physiology. This work offers a framework for future investigations to determine the specific physiological role and function of Mtb sugar transporters. Combined, this improved understanding of nutrient uptake and metabolism will inform future TB diagnostics and treatment. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | EMBO Travel Support Grant |
| Amount | € 300 (EUR) |
| Organisation | European Molecular Biology Organisation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 02/2020 |
| End | 02/2020 |
| Description | Flexible Talent Mobility Account 2 (FTMA2) |
| Amount | £28,014 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2020 |
| End | 10/2020 |
| Description | Microbiology Society Conference Grant 2018 |
| Amount | £240 (GBP) |
| Funding ID | GA000336 |
| Organisation | Microbiology Society |
| Sector | Learned Society |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 04/2018 |
| Description | Microbiology Society Conference Grant 2020 Round 1 |
| Amount | £390 (GBP) |
| Funding ID | GA001832 |
| Organisation | Microbiology Society |
| Sector | Learned Society |
| Country | United Kingdom |
| Start | 02/2020 |
| End | 02/2020 |
| Description | AMR Outreach Event - University of Warwick |
| 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 | 80 members of general public attended for a research visit to University of Warwick. I was responsible for one of the information stations, explaining how the fluorescence microscopy works, including examples from my own research. The visit sparked questions and discussion, and the feedback received from my audience reported increased understanding and interest in the studies of Mycobacterium tuberculosis. |
| Year(s) Of Engagement Activity | 2016 |
| Description | APPG TB (All Party Parliamentary Group on Global Tuberculosis) World TB Day 2016 Event at the Parliament |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Met with Nick Herbert MP and other MPs to highlight the importance of Global Fund replenishment. This had a real impact as the UK pledged a fantastic £1.1 billion in support of ending the AIDS/HIV, TB, and Malaria. Through its pledge to the Global Fund, the UK will help save 100 lives every hour from these deadly diseases. |
| Year(s) Of Engagement Activity | 2016 |
| Description | New Scientist Live - London Exhibition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | University of Warwick Science Department Exhibition during the New Scientist Live. The Exhibition included various games and activities for children as well as informative posters. We also gave out prices to competition winners. In particular, I spoke to general public about the tuberculosis research at University of Warwick. By explaining the global impact of tuberculosis and raising its profile, I challenged public assumptions about the infection. The event was very successful and our university has continued to participate in the following years. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://live.newscientist.com/new-scientist-live-2017?page=6 |
| Description | Skills Mentor |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Provided unbiased advice, direction and discussion for University of Warwick's MSc students related to the skills they will need as MSc students: communication, poster presentations, seminar presentations, research searches, literature searches, referencing/reference manager software etc. |
| Year(s) Of Engagement Activity | 2019,2020 |
| Description | University of Warwick Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | I spoke to prospective students and their parents/guardians, throughout the day, on the global impact of Mycobacterium tuberculosis, raising its profile and challenging public assumptions about the disease. I also explained the research we are conducting at Warwick to help fight TB. |
| Year(s) Of Engagement Activity | 2017 |
| Description | University of Warwick Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | I spoke to prospective students and their parents/guardians, throughout the day, on the global impact of Mycobacterium tuberculosis, raising its profile and challenging public assumptions about the disease. I also explained the research we are conducting at Warwick to help fight TB. |
| Year(s) Of Engagement Activity | 2019 |
| Description | World TB Day 2017 |
| 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 | An information stand in a local shopping centre in Coventry. Together with my research team, we spread awareness of tuberculosis burden globally but also locally in West Midlands. I spoke to general public about the symptoms, prevention, diagnosis and treatment of tuberculosis. I also explained the research we are conducting at University of Warwick to help fight TB. In addition, we offered games and competitions for the younger audience. I set up a collaboration with St Peter's Centre and FWT, a centre for woman for this event. These are not for profit organisations working with the local community, including refugees, and it allowed us to have a wider reach out. We provided them with information leaflets, which were then distributed in both centres. |
| Year(s) Of Engagement Activity | 2017 |
| Description | World TB Day 2018 |
| 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 organised two events for the World TB Day 2018. We had an information stand in the Coventry library and in the Herbert Art Gallery and Museum on separate days. Together with my research team, we spread awareness of tuberculosis burden globally but also locally in West Midlands. I spoke to general public about the symptoms, prevention, diagnosis and treatment of tuberculosis. I also explained the research we are conducting at University of Warwick to help fight TB. For the younger audience, we offered games on iPads to teach them the concept of antibiotic resistance. |
| Year(s) Of Engagement Activity | 2018 |
| Description | World TB Day 2019 |
| 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 | The laboratory held an information/demonstration stand for World TB Day. This event was held at the Coventry central library. This led to lots of interesting discussions around TB, the research that we are doing and what we need to do to eradicate this pathogen. |
| Year(s) Of Engagement Activity | 2019 |