Antimicrobial resistance in gram negative bacterial is a growing problem in hospitals. Resistance genes providing protection against antibiotics and other infection control agents such as biocides reside on plasmids as a result of selection and survival of resistant hosts. Recent studies have uncovered E. coli strains in river sediment downstream of a sewage treatment plant which partly reflects the gut microbiome of the population served by the treatment plant. Whilst many strains were commensal E. coli over 10% belonged to well defined sequence types (STs) and carried known virulence determinants in addition to readily transferrable plasmids with a range of antimicrobial resistance genes (ARGs). Some strains were identified as ST131, a common cause of urinary tract infections in hospitals. Plasmids harbouring the extended spectrum beta-lactamase gene blaCTX-M-15 have been implicated in increasing fitness and virulence of this host. Whilst the widely held hypothesis for plasmid persistence relates to the selective advantage offered by adaptive genes carried, other data on SNP analysis of host genomes indicated changes in host relating to fitness in addition to plasmid changes caused by IS26 activity. The strains recovered from sewage treatment and from anaerobic digestion biosolids (on farms) will form the basis for studies of host-plasmid adaptation and implications for ARG persistence. The objectives are:
1. Investigate ARG profiles of selected E. coli strains from human and animal origin carrying blaCTX-M-15 and determine plasmid persistence in chemostat under different growth regimes.
2. Introduce plasmids studied in (1) into a range of commensal and lab strains of E. coli for analysis of plasmid persistence and host evolution under varying regimes of growth rate and selection.
3. Study mechanisms of plasmid adaptation and fate of ARG to evaluate approaches to reducing ARG carriage in the normal gut microbiome.