Antimicrobial resistance transmission in the environment: the role of soil as a reservoir and conduit in the transmission of AMR
This PhD project will use a multi-method approach, including methods in microbiology, molecular biology and bioinformatics, to evaluate the importance of the soil as an environmental reservoir and conduit for the transmission of antibiotic resistant bacteria and drug resistant genes such as b-lactamase genes.
This call is for self-funded students.
Antimicrobial resistance (AMR) is an on-going global health threat; and similar to the SARS-CoV-2 pandemic, has a significant impact on public health and the global economy. If no action is taken, an estimated 10 million deaths per annum will arise from infections caused by resistant microorganisms by 20501,2. It is now widely recognised that global efforts to control the spread of resistant microorganisms must utilise a One Health-based approach. This approach permits a collaborative examination of how resistant pathogens can spread between humans, animals and the environment3.
The contamination of the environment, specifically water bodies and soil, by antimicrobials, including antibiotic resistant bacteria (ABR) and antibiotic resistance genes (ARG), is attributable to human activity4. These include the disposal of human and animal waste5,6, pharmaceutical manufacturing waste7, and use of antimicrobials as pesticides in crops8,9.
The presence of ABR and ABG in the environment increases the potential for onwards dissemination, colonisation and establishment of infection in human and animal populations4.
Many bacteria which are implicated in important, and recalcitrant human and animal infections have been isolated in water bodies and the soil10. Amongst these are Enterobacteriaceae, which are ubiquitous and members are commensal and/or pathogenic gut dwellers (enteric bacteria). Species such as E. coli and Klebsiella spp. are commonly associated with important resistance genes, including extended spectrum b-lactamase (ESBLs) and carbapenemases (CPEs) that confer resistance to third generation cephalosporins and the carbapenem antibiotics, respecively11. Although there is ample evidence-based information on the global spread of these clinically important resistant enteric bacteria in human12,13 and animal populations14,15, the potential for soil as an environmental reservoir is understudied. There are gaps in our understanding of the impact of ABR and ABGs in the soil and the risk this poses to human and animal health16. Thus, more research is needed to address these knowledge gaps and evaluate the risks to human, animal and environmental health17.
Therefore, this PhD project will use a multi-method approach to evaluate the importance of the soil as a reservoir and conduit for the transmission of antibiotic selected resistant enteric bacteria and selected b-lactamase genes (including ESBLs and CPEs). Specifically, the student will receive training in the use of a selection of culture- and PCR-based profiling, 16sRNA, single-genome and metagenome sequencing and analyses to answer the research questions.
Testable hypothesis -The project will test the hypothesis that soil stratification/structure facilitates the persistence of ABR and the ARGs they carry. On perturbation, this persistence effect is reduced, potentiating the loss and subsequent spread of ARGs via host ARB.
This will be achieved by using an in vitro soil strata model and soil and water samples obtained from large commercial farms to evaluate the following:
- How effective is soil as a reservoir for AMR?
- Does AMR persist in the soil?
- Does AMR spread from the soil to the wider environment, and onwards to humans and animals?
- What components of soil are important for AMR transmission?
- The role in facilitating onward transmission to humans and animals?
- How does perturbation affect distribution of AMR in the soil?
- Does (a) above induce dissemination/how does transmission occur?
This project will equip you with key microbiology, molecular biology and bioinformatics (bacterial genome analyses and metagenomics skills). You will be part of large research groups jointly working on antimicrobial resistance across the Schools of Biosciences and Medicine and Veterinary Medicine and you will have the opportunity to make an impact on a project that has an international and interdisciplinary outlook.
Recent relevant references
1 O’Neil, J. Antimicrobial Resistance: tackling a crises for the health and wealth of Nations. (December 2014, 2014).
2 O’Neill, J. Tackling Drug-resistant infections globally: Final Report and Recommendations. (2016).
3 Courtenay, M., Sweeney, J., Zielinska, P., Brown Blake, S. & La Ragione, R. One Health: An opportunity for an interprofessional approach to healthcare. J Interprof Care 29, 641-642, doi:10.3109/13561820.2015.1041584 (2015).
4 Finley, R. L. et al. The scourge of antibiotic resistance: the important role of the environment. Clin Infect Dis 57, 704-710, doi:10.1093/cid/cit355 (2013).
5 Hocquet, D., Muller, A. & Bertrand, X. What happens in hospitals does not stay in hospitals: antibiotic-resistant bacteria in hospital wastewater systems. J Hosp Infect 93, 395-402, doi:10.1016/j.jhin.2016.01.010 (2016).
6 Jechalke, S., Heuer, H., Siemens, J., Amelung, W. & Smalla, K. Fate and effects of veterinary antibiotics in soil. Trends Microbiol 22, 536-545, doi:10.1016/j.tim.2014.05.005 (2014).
7 Larsson, D. G. Pollution from drug manufacturing: review and perspectives. Philos Trans R Soc Lond B Biol Sci 369, doi:10.1098/rstb.2013.0571 (2014).
8 McManus, P. S., Stockwell, V. O., Sundin, G. W. & Jones, A. L. Antibiotic use in plant agriculture. Annu Rev Phytopathol 40, 443-465, doi:10.1146/annurev.phyto.40.120301.093927 (2002).
9 Blau, K. et al. The Transferable Resistome of Produce. mBio 9, doi:10.1128/mBio.01300-18 (2018).
10 Ekwanzala, M. D., Dewar, J. B., Kamika, I. & Momba, M. N. B. Systematic review in South Africa reveals antibiotic resistance genes shared between clinical and environmental settings. Infect Drug Resist 11, 1907-1920, doi:10.2147/IDR.S170715 (2018).
11 Iredell, J., Brown, J. & Tagg, K. Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications. BMJ 352, h6420, doi:10.1136/bmj.h6420 (2016).
12 Okoro, C. K. et al. Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa. Nat Genet 44, 1215-1221, doi:10.1038/ng.2423 (2012).
13 Chattaway, M. A. et al. Fluoroquinolone-Resistant Enteric Bacteria in Sub-Saharan Africa: Clones, Implications and Research Needs. Front Microbiol 7, 558, doi:10.3389/fmicb.2016.00558 (2016).
14 Hornsey, M. et al. Characterization of a colistin-resistant Avian Pathogenic Escherichia coli ST69 isolate recovered from a broiler chicken in Germany. J Med Microbiol 68, 111-114, doi:10.1099/jmm.0.000882 (2019).
15 Liakopoulos, A. et al. Occurrence and characterization of extended-spectrum cephalosporin-resistant Enterobacteriaceae in healthy household dogs in Greece. J Med Microbiol 67, 931-935, doi:10.1099/jmm.0.000768 (2018).
16 Huijbers, P. M. et al. Role of the Environment in the Transmission of Antimicrobial Resistance to Humans: A Review. Environ Sci Technol 49, 11993-12004, doi:10.1021/acs.est.5b02566 (2015).
17 Aga, D. D., J, Gandra, S, Kasprzyk-Hordern, B, Larsson, J, McLain, J, Singer, A, Snape, J, Slijkhuis, H, Sweetman , A & Voulvoulis, N. Initiatives for Addressing Antimicrobial Resistance in the Environment: Current Situation and Challenges. (2018).
18 Giles M, Cawthraw SA, AbuOun M, Thomas CM, Munera D, Waldor MK, La Ragione RM, Ritchie JM. 2018. Host-specific differences in the contribution of an ESBL IncI1 plasmid to intestinal colonization by Escherichia coli O104:H4. J Antimicrob Chemother. 2018 Feb 28. doi: 10.1093/jac/dky037.
19. Liakopoulos A, La Ragione RM, Nagel C, Schatzschneider U, Rozen DE, Betts JW. 2020. Manganese complex [Mn(CO)3(tpa-κ3N)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus pneumoniae. J Glob Antimicrob Resist. S2213-7165(20)30124-7.
20. Güntzel P, Nagel C, Weigelt J, Betts JW, Pattrick CA, Southam HM, La Ragione RM, Poole RK, Schatzschneider U. 2019. Biological activity of manganese(i) tricarbonyl complexes on multidrug-resistant Gram-negative bacteria: From functional studies to in vivo activity in Galleria mellonella. Metallomics. 11(12):2033-2042. doi: 10.1039/c9mt00224c. CR
21. Betts JW, Hornsey M, Higgins PG, Lucassen K, Wille J, Salguero FJ, Seifert H, La Ragione RM. 2019. Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa. J Med Microbiol. PR
First Class or Upper Second-class BSc or in Master’s level degree (or international equivalent, merit or disntnction) in Microbiology, Molecular Biology, Biomedical Sciences, Veterinary Biosciences or related fields.
Prior experience in research or industry may also be acceptable.
IELTS Academic: 6.5 or above (or equivalent) with 6 in each individual category.