Characterization of Relationships Between Fluoroquinolone-Resistant E. coli from Humans, Dogs, and Dairy Cattle Living in South West England

  • Oliver J Mounsey

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Escherichia coli are a common component of the mammalian gut microflora. E. coli are also frequent intestinal and extraintestinal pathogens, which cause diarrhoea, urinary tract infection, cystitis, pyelonephritis, sepsis, and meningitis, in humans, as well as mastitis, in dairy cattle, and severe respiratory and systemic disease in chickens, and which frequently carry multiple antibacterial resistance (ABR) genes. This project sought to investigate the transmission of fluoroquinolone resistant (FQ-R) E. coli between three important reservoirs – humans, dairy cattle, and companion animals (16-week-old dogs) within a 50 x 50 km study region in the South West of England. To do this, E. coli isolated from faecally-contaminated near-cattle environments, human urine samples submitted for diagnostic microbiology, and puppy faeces, were subjected to detailed molecular epidemiology investigation. Risk factors for the carriage of (FQ-R) E. coli in dogs and dairy cattle were also investigated.
Isolates from all three reservoirs were analysed by multiplex PCR and a subset were subjected to whole genome sequencing (WGS). This enabled a thorough analysis of ABR and virulence gene carriage, sequence typing (ST), and mutations in the quinolone resistance determining regions (QRDR) of gyrA/B and parC/E. Whole-genome sequencing also enabled single nucleotide polymorphism variant calling for SNP-distance and phylogenetic analysis.
Significant associations were found in the human urinary isolates between carriage of genes associated with ABR (aac(6’)Ib-cr, blaOXA-1, blaCTX-M-15, tet(A), and aac(3)-IIa) and virulence (cnf1, iss, and nfaE). Raw feeding was identified as a significant risk factor for carriage of FQ-R E. coli in dogs. Fluoroquinolone use on a farm was positively associated with the odds of finding FQ-R E. coli in faeces from cattle suggesting that reducing use may lead to a reduction in FQ-R in dairy farms. Dry cow therapy – antibacterial injected into the udder – was found to be negatively associated with FQ-R E. coli in dairy cattle, and we showed that this was likely to be because FQ-R E. coli are rarely resistant to the antibacterial agents found within dry cow therapy. Hence, dry cow therapy could be manipulated to reduce the prevalence of other types of resistance.
Most importantly, closely related FQ-R E. coli, differing by <30 SNPs, were found in all three reservoirs, which is suggestive of sharing between dogs, humans, and dairy cattle within the study region. This was only true for certain STs, particularly important are ST162 and ST744.
Date of Award28 Sep 2021
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorMatthew B Avison (Supervisor) & Tristan A Cogan (Supervisor)

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