PhD Research Project: NERC CENTA - Predicting the fate of resistance genes, plasmids and hosts in m

Location
United Kingdom
Posted
Nov 30, 2016
Closes
Jan 23, 2017
Organization Type
University and College
Hours
Full Time
Details

Project Highlights:
• Effect of biodiversity on fate of resistance plasmids: are there preferential transfer paths? How would that affect risk analysis?
• Can we predict persistence of resistance based on transfer rates and fitness costs? Or do we need to include co-evolution of plasmids and hosts?
• Is inhibition of plasmid transfer the most effective way to reduce resistance?

Overview:
The widespread use of antibiotics in human and veterinary medicine and as growth promoters in agriculture has not only selected for resistance genes but also for plasmids carrying resistance genes. As a result, plasmids as vectors of resistance genes have become prevalent, enhancing the rate of aquisition and dissemination of any new resistance genes as soon as new antimicrobials are introduced. Likewise, the simultaneous or alternating presence of several antimicrobials has selected for insertion sequence elements (IS) and other mobilizers of genes as they facilitate the accumulation of multiple resistances on single plasmids. Together, this has increased the potential for pathogens to aquire new resistances and new combinations of resistances. Multidrug resistant pathogens have brought us back to the pre-antibiotic era.

Hotspots of resistance genes in the environment are wastewater treatment plants and animal manures and slurrys on farms, which are being spread on arable land. Runoff from these fields and effluent from wasterwater treatment enter rivers and river sediments, also untreated sewage is discharged into rivers through storm overflow drains.

The group of Prof Wellington has isolated numerous Escherichia coli strains from river sediments. They carry a range of different types (IncF, IncA/C, IncQ) of plasmids with various resistance genes, eg the extended spectrum beta-lactamase blaCTX-M-15. Most of these strains are commensals but more than 10% carry virulence genes and resistance plasmids and are well known pathogens such as ST131, a common cause of urinary tract infections in hospitals, clearly linking human pathogens to environmental reservoirs.

We will use simple mass-action and more powerfull individual-based models to understand and predict the fate of resistance plasmids in mixed communities of several E. coli strains. The models will be based on plasmid transfer rates and fitness costs measured by a MIBTP PhD student in the Wellington lab (Victoria Clark) who has just started to investigate plasmid dynamics in chemostats and is co-supervised by Dr Kreft. She will be one year ahead of this joint modelling project, which will enable the modelling to feed into the experiments and the data to feed into the modelling.

Funding Notes

In addition to completing an online application form, you will also need to complete and submit the CENTA studentship application form available from www.centa.org.uk.

CENTA studentships are for 3.5 years and are funded by the Natural Environment Research Council (NERC). In addition to the full payment of their tuition fees, successful candidates will receive the following financial support.

Annual stipend, set at £14,296 for 2016/17
Research training support grant (RTSG) of £8,000

CENTA students are required to undertake from 45 days training throughout their PhD including a 10 day placement.

References

Merkey BV, Lardon LA, Seoane JM, Kreft J-U, Smets BF. 2011. Growth dependence of conjugation explains limited plasmid invasion in biofilms: an individual-based modelling study. Environ Microbiol 13:2435–2452.

Kreft J-U. 2014. Mathematical modelling of plasmid dynamics. In: Bell E et al. (eds.), Molecular Life Sciences: An Encyclopedic Reference. Springer-Verlag, Berlin Heidelberg.

Hellweger FL, Clegg RJ, Clark JR, Plugge CM, Kreft J-U. 2016. Advancing microbial sciences by individual-based modelling. Nat Rev Micro 14:461–471.

Amos GCA, Hawkey PM, Gaze WH, Wellington EM. 2014. Waste water effluent contributes to the dissemination of CTX-M-15 in the natural environment. J Antimicrob Chemother 69:1785–1791.

Amos GCA, Zhang L, Hawkey PM, Gaze WH, Wellington EM. 2014. Functional metagenomic analysis reveals rivers are a reservoir for diverse antibiotic resistance genes. Vet Microbiol 171:441–447.

Lehmann K, Bell T, Bowes MJ, Amos GCA, Gaze WH, Wellington EMH, Singer AC. 2016. Trace levels of sewage effluent are sufficient to increase class 1 integron prevalence in freshwater biofilms without changing the core community. Water Res 106:163–170.