Antibiotic resistance genes are frequently carried on plasmids, which spread horizontally between bacteria and vertically through expansion of successful resistant clones. Yet for many Enterobacterales, in livestock, the farm environment and as human commensals, we often do not know the relative contributions of plasmid transfer and clonal expansion to maintaining resistance.

Most epidemiological models of drug-resistant bacteria do not track plasmid identity and dynamics explicitly, while theoretical models of plasmid dynamics usually operate at the bacterial-population scale. Few models connect within-host processes such as conjugation, establishment, segregational loss and competition with resident strains to transmission and resistance prevalence between hosts and reservoirs. These processes determine whether a plasmid transfers into a new lineage, establishes there and subsequently persists.

Consequently, we cannot explain why particular plasmid–lineage combinations become common whereas others do not. Prominent examples include IncF plasmids carrying blaCTX-M-15 in Escherichia coli ST131-C2, IncI1 plasmids carrying blaCTX-M-1 in livestock-associated E. coli and Salmonella, and IncHI2 plasmids carrying mcr-1 in livestock-associated Enterobacterales. These associations may reflect differences in transfer, initial establishment, long-term persistence or subsequent clonal expansion. Population genomics identifies successful plasmid–lineage associations but often cannot fully resolve whether they arise through repeated transfer, differential loss or expansion of successful clones. Laboratory studies measure processes such as conjugation, fitness costs and plasmid stability, but seldom link them directly to epidemic potential or resistance prevalence under antimicrobial selection.

This project will determine which plasmid–host combinations allow plasmid-associated resistance genes (pARGs) to become epidemic, and whether this can be predicted from antimicrobial selection and plasmid–lineage interactions affecting transfer, establishment and persistence, rather than from plasmid or lineage characteristics alone. We will test whether these properties of plasmid–host associations generalise across agricultural, environmental and clinical reservoirs.

The project methodology can be tailored to the candidate's interests:

Modelling: developing a multi-scale model coupling within- and between-host processes and distinguishing plasmid transfer from clonal expansion.
Experimental: measuring conjugation, establishment, fitness cost and loss across a panel of plasmid–lineage combinations spanning animal- and human-associated hosts, and testing for non-additive plasmid–lineage effects.
Genomic: using a novel longitudinal dataset of Enterobacterales from animal, environmental and clinical sources, including important Klebsiella pneumoniae lineages such as ST11, ST258 and ST23, to infer acquisition events and distinguish repeated plasmid transfer from clonal expansion using dated chromosomal phylogenies and resolved plasmid sequences.
Combined: integrating experimental or genomic estimates directly into a mathematical model.
Findings will identify which plasmid–host combinations sustain resistance and determine the processes responsible, helping to target surveillance and antimicrobial use across animal, environmental and clinical reservoirs.

This project would suit a student interested in microbial evolution and infectious disease dynamics. Applicants with a background in mathematical modelling, microbial genomics or experimental microbiology are particularly encouraged, as are those wishing to work across these areas. Full training will be provided in unfamiliar techniques.