Resilience and resistance: the interplay between antibiotic resistance and pathogen resilience outside of the host

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

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.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1642949 Studentship BB/M01116X/1 05/10/2015 27/12/2020 Victoria Louise Clark
 
Description Using long read sequencing, have resolved a large environmentally isolated multi-resistant plasmid. this was found to be missing a large section of its core genes that allow it to transfer to other bacteria, allowing it to collect many different resistance genes but essentially embedding itself into just one bacterial host. This appears to be the first time this specific genomic streamlining has been reported
Exploitation Route Understanding the genetic mechanisms involved in multi-resistance plasmids transferring and persisting within new hosts in the environment is essential before mitigation strategies can be developed.
Sectors Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description public outreach event- "the microbes on us and around us" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact held in the SLS atrium, there were a number of talks given by academics and a poster presentation/discussion with the public talking to researchers in the area (such as myself) and talking about their work in the area.
Year(s) Of Engagement Activity 2017
URL https://warwick.ac.uk/fac/sci/lifesci/outreach/pastevents/