About the project

Antimicrobial resistance (AMR) is a serious global health problem, which can lead to untreatable bacterial infections. AMR genes can be easily shared between bacteria on transmissible elements such as plasmids. AMR plasmids can carry a variety of resistance genes, and transfer of these plasmids can cause difficult to treat infections. Particularly problematic are carbapenem resistant Klebsiella pneumoniae, and extended-spectrum beta-lactam resistant Escherichia coli. Pathogens with plasmids carrying AMR genes are responsible for some of the most difficult to treat and often multi-drug resistant infections.

A key hotspot for the transmission of AMR between bacteria is the gastrointestinal (GI) microbiome. For example, AMR genes can be acquired after travel to countries with high AMR levels, or after medical care. This makes the microbiome an important reservoir of AMR, and a key environment where AMR transmission is likely to occur.

We propose using a combination of classical microbiology, fluorescent based techniques, and genomics to monitor AMR plasmid dynamics within a state-of-the-art multi-vessel bioreactor model of the colonic microbiome.

Specifically, this project will explore how fluorescently tagged AMR plasmids persist, transmit, and evolve within the human microbiome. We will explore the microbiome-produced factors which influence AMR plasmid dynamics. Together this project will help to disentangle how AMR transmission in the microbiome occurs and contribute to our efforts to minimise the impacts of AMR.

Please contact Dr. Buckner for further information about the project.

References

1. Buckner MM, Saw HT, Osagie RN, McNally A, Ricci V, Wand ME, Woodford N, Ivens A, Webber MA, Piddock LJ. Clinically relevant plasmid-host interactions indicate transcriptional not genomic modifications ameliorate fitness costs of KPC carrying plasmids. 2018. mBio vol. 9 no. 2 e02303-17 doi: 10.1128/mBio.02303-172.
2. Buckner MM, Ciusa ML, Meek RW, Moorey AR, McCallum GE, Prentice EL, Reid JP, Alderwick L, Di Maio A, Piddock LJ. HIV drugs inhibit transfer of plasmids carrying extended-spectrum-lactamase and carbapenemase genes. 2020. mBio Vol 11 no 1 e03355-19 doi 10.1128/mBio.03355-193.
3. Alav I, Pordelkhaki P, de Resende PE, Partington H, Gibbons S, Lord R, Buckner MM. 2023. Metal complexes and conjugation: Harnessing the power of cobalt complexes to curtail plasmid transfer. bioRxiv. Doi: 10.1101/2023.11.24.5685734.
4. Element SJ, Moran RA, Beattie E, Hall RJ, van Schaik W, Buckner MM. 2023. Growth in a biofilm promotes conjugation of a blaNDM-1-bearing plasmid between Klebsiella pneumoniae strains. mSphere, doi: 10.1128/msphere.00170-235.
5. Kessler C, Hou J, Neo O, Buckner M. AMR plasmid conjugation in the gut microbiome. 2023. FEMS Microbiology Reviews, Vol 47, Issue 1, doi: 10.1093/femsre/fuac0446.
6. Horniblow, R. D., Henesy, D., Iqbal, T. H. & Tselepis, C. Modulation of iron transport, metabolism and reactive oxygen status by quercetin–iron complexes in vitro. Molecular nutrition & food research 61, 1600692 (2017).
7. Horniblow, R. D. et al. The chelation of colonic luminal iron by a unique sodium alginate for the improvement of gastrointestinal health. Molecular nutrition & food research 60, 2098-2108 (2016).
8. Horniblow, R. D. et al. The safety and tolerability of a potential alginate-based iron chelator; results of a healthy participant study. Nutrients 11, 674 (2019).
9. Horniblow, R. D., Pathak, P., Eshrati, M., Latunde-Dada, G. O. & Tselepis, C. Intestinal iron bio-accessibility changes by Lignin and the subsequent impact on cell metabolism and intestinal microbiome communities. Food & Function 14, 3673-3685 (2023).
10. Goelen, J. et al. Quantification of fluid volume and distribution in the paediatric colon via magnetic resonance imaging. Pharmaceutics 13, 1729 (2021).
11. Reyman, M., van Houten, M.A., Watson, R.L., Chu, M.L.J.N., Arp, K., de Waal, W.J., Schiering, I., Plötz, F.B., Willems, R.J.L., van Schaik, W., Sanders, E.A.M., Bogaert, D., 2022. Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial. Nat. Commun. 13, 893. 
12. McInnes, R.S., uz-Zaman, M.H., Alam, I.T., Ho, S.F.S., Moran, R.A., Clemens, J.D., Islam, M.S., van Schaik, W., 2021. Metagenome-Wide Analysis of Rural and Urban Surface Waters and Sediments in Bangladesh Identifies Human Waste as a Driver of Antibiotic Resistance. mSystems 6, e00137-21.
13. Doughty EL, Liu H, Moran RA, Hua X, Ba X, Guo F, Chen X, Zhang L, Holmes M, van Schaik W, McNally A, Yu Y. 2023. Endemicity and diversification of carbapenem-resistant Acinetobacter baumannii in an intensive care unit. Lancet Reg Health West Pac. 9:37.
14. McCallum GE, Rossiter AE, Quraishi MN, Iqbal TH, Kuehne SA, van Schaik W. 2023. Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts. Microb Genom.9(6):mgen001030.

Entry Requirements

Applicants should have a strong background in microbiology, and ideally a background in bioinformatics, immunology and/or biochemistry. They should have a commitment to research in microbiology and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a related field, including but not limited to: Biomedical Science, Microbiology, Immunology, Biochemistry.

What does the scholarship provide?

1. Financial Support: Recipients of these scholarships will receive substantial financial support, including a stipend at UKRI rates, which is set at £18,622 per year. This support covers tuition fees, living expenses, and research-related costs, including bench fees. This support is designed to alleviate the financial burden often associated with pursuing a doctoral degree.
2. Mentorship and Guidance: Scholarship recipients will benefit from mentorship opportunities and guidance from accomplished faculty members who are dedicated to helping them succeed in their academic and research endeavours.
3. Research Opportunities: We are committed to providing an exceptional research environment. Students will have access to state-of-the-art facilities, cutting-edge resources, and a vibrant scholarly community.
4. Community Building: A key component of the scholarship programme is the creation of a supportive community of Black British researchers pursuing PhDs. This network will foster collaboration and peer support among scholars.
5. Research Training Support Grant: In addition to financial support, scholarship recipients will receive a research training support grant. This grant is intended to support conference attendance, fieldwork, and other essential activities that enhance their research and academic growth.
6. Commitment to Inclusivity: We are dedicated to building an inclusive academic environment that values diversity and ensures equitable access to education.

Contact the lead supervisor

Once applicants have familiarised themselves with the above project details, they are encouraged to contact the lead PhD supervisor to discuss the project and the applicant's suitability for the project. This is recommended before you submit an application to the PhD project.

Application portal tips

• You don’t need to complete your application in one session. Simply save it and come back to it when you’re ready.
• Avoid delays by checking all your information is accurate and complete.
• Your application won’t be processed until you’ve completed all the relevant sections and submitted it.
• If you run into any technical issues with your application, email us at directapplicationsystem@contacts.bham.ac.uk

What happens next?

Once you’ve submitted your application, we’ll send you details on how to access your applicant portal. You’ll be able to track the progress of your application, update your personal information, view decisions and accept offers.

Your application will be ‘pending’ on your portal while we check your application.

You can add or edit some details or documents within your application after it’s been submitted through your applicant portal. Or email pgadmissions@contacts.bham.ac.uk (include your applicant ID number) and we can add or edit for you.