title: Genetic & virulence profiling of ESBL-positive E. coli from nosocomial & veterinary sources.
abstract: CTX-M genes are the most prevalent ESBL globally, infiltrating nosocomial, community and environmental settings. Wild and domesticated animals may act as effective vectors for the dissemination of CTX-producing Enterobacteriaceae. This study aimed to contextualise blaCTX-M-14-positive, cephalosporin-resistant Enterobacteriaceae human infections and compared resistance and pathogenicity markers with veterinary isolates. Epidemiologically related human (n=18) and veterinary (n=4) blaCTX-M-14-positive E. coli were fully characterised. All were typed by XbaI pulsed field gel electrophoresis and ST. Chromosomal/plasmidic locations of blaCTX-M-14 were deduced by S1-nuclease digestion, and association with ISEcp1 was investigated by sequencing. Conjugation experiments assessed transmissibility of plasmids carrying blaCTX-M-14. Presence of virulence determinants was screened by PCR assay and pathogenicity potential was determined by in vitro Galleria mellonella infection models. 84% of clinical E. coli originated from community patients. blaCTX-M-14 was found ubiquitously downstream of ISEcp1 upon conjugative plasmids (25-150 kb). blaCTX-M-14 was also found upon the chromosome of eight E. coli isolates. CTX-M-14-producing E. coli were found at multiple hospital sites. Clonal commonality between patient, hospitals and livestock microbial populations was found. In vivo model survival rates from clinical isolates (30%) and veterinary isolates (0%) were significantly different (p<0.05). Co-transfer of blaCTX-M-14 and virulence determinants was demonstrated. There is evidence of clonal spread of blaCTX-M-14-positive E. coli involving community patients and farm livestock. blaCTX-M-14 positive human clinical isolates carry a lower intrinsic pathogenic potential than veterinary E. coli highlighting the need for greater veterinary practices in preventing dissemination of MDR E. coli among livestock.
authors.affiliation: Department of Medical Microbiology & Infectious Disease, Heath Hospital, Cardiff CF14 4XW, UK. Electronic address: tyrrelljm@cardiff.ac.uk.
authors.forename: J M
authors.initials: JM
authors.lastname: Tyrrell
authors.affiliation: Public Health Wales Microbiology Cardiff, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK.
authors.forename: M
authors.initials: M
authors.lastname: Wootton
authors.affiliation: Department of Medical Microbiology & Infectious Disease, Heath Hospital, Cardiff CF14 4XW, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Toleman
authors.affiliation: Department of Medical Microbiology & Infectious Disease, Heath Hospital, Cardiff CF14 4XW, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Howe
authors.affiliation: Department of Food & Nutritional Studies, University of Reading, RG6 6AP, UK.
authors.forename: M
authors.initials: M
authors.lastname: Woodward
authors.affiliation: Department of Medical Microbiology & Infectious Disease, Heath Hospital, Cardiff CF14 4XW, UK.
authors.forename: T R
authors.initials: TR
authors.lastname: Walsh
mesh_terms: D000818:Animals; D003227:Conjugation, Genetic; D003428:Cross Infection / Q000382:microbiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D006801:Humans; D010957:Plasmids / Q000235:genetics; D014774:Virulence / Q000235:genetics*
keywords: CTX-M-14; E. coli; ESBL (Extended spectrum beta-lactamases); Pathogenicity; Virulence